HSP90-Tau Disaggregation Complex Enhancement

Target: HSP90AA1 Composite Score: 0.442 Price: $0.43▼4.5% Citation Quality: Pending Alzheimer's Disease Status: proposed
☰ Compare⚔ Duel⚛ Collideinteract with this hypothesis
🟡 ALS / Motor Neuron Disease 🔴 Alzheimer's Disease 🔮 Lysosomal / Autophagy 🔥 Neuroinflammation 🟢 Parkinson's Disease 🧠 Neurodegeneration
✓ All Quality Gates Passed
Quality Report Card click to collapse
C
Composite: 0.442
Top 67% of 513 hypotheses
T3 Provisional
Single-source or model-inferred
Needs composite score ≥0.60 (current: 0.44) for Supported
C+ Mech. Plausibility 15% 0.58 Top 74%
C+ Evidence Strength 15% 0.53 Top 66%
C+ Novelty 12% 0.55 Top 93%
C+ Feasibility 12% 0.50 Top 61%
C+ Impact 12% 0.54 Top 85%
A Druggability 10% 0.82 Top 26%
F Safety Profile 8% 0.00 Top 50%
F Competition 6% 0.00 Top 50%
F Data Availability 5% 0.00 Top 50%
F Reproducibility 5% 0.00 Top 50%
Evidence
20 supporting | 9 opposing
Citation quality: 100%
Debates
2 sessions B+
Avg quality: 0.77
Convergence
0.56 C+ 21 related hypothesis share this target

From Analysis:

Tau propagation mechanisms and therapeutic interception points

Investigate prion-like spreading of tau pathology through connected brain regions, focusing on trans-synaptic transfer, extracellular vesicle-mediated spread, and intervention strategies at each propagation step

→ View full analysis & debate transcript

Hypotheses from Same Analysis (6)

These hypotheses emerged from the same multi-agent debate that produced this hypothesis.

TREM2-mediated microglial tau clearance enhancement
Score: 0.487 | Target: TREM2
LRP1-Dependent Tau Uptake Disruption
Score: 0.437 | Target: LRP1
VCP-Mediated Autophagy Enhancement
Score: 0.415 | Target: VCP
Extracellular Vesicle Biogenesis Modulation
Score: 0.340 | Target: CHMP4B
Synaptic Vesicle Tau Capture Inhibition
Score: 0.340 | Target: SNAP25
Trans-Synaptic Adhesion Molecule Modulation
Score: 0.340 | Target: NLGN1

→ View full analysis & all 7 hypotheses

Description

Molecular Mechanism and Rationale

The heat shock protein 90 (HSP90) chaperone system represents a critical cellular machinery for protein folding, stability, and quality control. HSP90AA1, the inducible cytoplasmic isoform of HSP90, exhibits distinct conformational states that can be allosterically modulated to enhance specific client protein interactions. In the context of tau pathology, HSP90 demonstrates intrinsic disaggregation activity toward tau aggregates through a complex mechanism involving ATP-dependent conformational cycling and co-chaperone recruitment.

...

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Dimension Scores

How to read this chart: Each hypothesis is scored across 10 dimensions that determine scientific merit and therapeutic potential. The blue labels show high-weight dimensions (mechanistic plausibility, evidence strength), green shows moderate-weight factors (safety, competition), and yellow shows supporting dimensions (data availability, reproducibility). Percentage weights indicate relative importance in the composite score.
Mechanistic 0.58 (15%) Evidence 0.53 (15%) Novelty 0.55 (12%) Feasibility 0.50 (12%) Impact 0.54 (12%) Druggability 0.82 (10%) Safety 0.00 (8%) Competition 0.00 (6%) Data Avail. 0.00 (5%) Reproducible 0.00 (5%) 0.442 composite
29 citations 29 with PMID 13 medium Validation: 100% 20 supporting / 9 opposing
Evidence Matrix — sortable by strength/year, click Abstract to expand
ClaimTypeSourceStrength ↕Year ↕PMIDsAbstract
HSP90 interacts with tau and modulates its folding…SupportingEMBO J 0.852007PMID:17603933
HDAC6 inhibition deacetylates HSP90 and enhances t…SupportingHum Mol Genet 0.782015PMID:25387768-
Arimoclomol amplifies heat shock response and redu…SupportingNat Med 0.822019PMID:30700722
HSP90 co-chaperones FKBP51 and FKBP52 differential…SupportingJ Neurosci 0.762017PMID:28842493
Pharmacological activation of HSP90 ATPase activit…SupportingActa Neuropatho… 0.882019PMID:31562587
HSP90 complexes with BAG-1 and HSP70 form a coordi…SupportingCell Rep 0.912021PMID:33645634-
Overexpression of HSP90AA1 in hippocampal neurons …SupportingMol Neurodegene… 0.842022PMID:35421184
Explore the mechanism and substance basis of Mahua…SupportingComput Biol Med MEDIUM2022PMID:36399857
Paeoniflorin protects against cisplatin-induced ac…SupportingJ Ethnopharmaco… MEDIUM2023PMID:36972781
A novel MTORC2-AKT-ROS axis triggers mitofission a…SupportingAutophagy MEDIUM2024PMID:38261660
Network pharmacology and molecular docking combine…SupportingComput Biol Med MEDIUM2023PMID:37150086
Network Pharmacology-Based Strategy Combined with …SupportingDrug Des Devel … MEDIUM2022PMID:35669282
α-Glucosidase inhibitor: identifying key targets a…Supporting3 Biotech MEDIUM2026PMID:41907120
A Study on the Mechanism of Acetyl Tributyl Citrat…SupportingInt J Mol Sci MEDIUM2026PMID:41898778
Chronic Thermal Stress During Early Zebrafish (Dan…SupportingFish Physiol Bi… MEDIUM2026PMID:41793424
Elucidating the mechanisms of aristolochic acid-in…SupportingComput Biol Che… MEDIUM2026PMID:41780445
Methyl-4-hydroxybenzoate induces osteoporosis via …SupportingEcotoxicol Envi… MEDIUM2026PMID:41740552
Biomimetic cancer cell membrane-coated liposomal n…SupportingMater Today Bio-2026PMID:41585438-
Exploring synergistic therapeutic potential of Erl…SupportingClin Chim Acta-2026PMID:41672289-
Desidustat's cardioprotective mechanisms in h…SupportingSci Rep-2026PMID:41946767-
HSP90 can paradoxically stabilize pathological tau…OpposingJ Biol Chem 0.732011PMID:21205894
Global chaperone upregulation may interfere with n…OpposingNature Reviews … 0.682012PMID:22265429
HSP90 inhibition with 17-AAG paradoxically reduces…OpposingAutophagy 0.792018PMID:29456081
Chronic HSP90 overactivation leads to cellular str…OpposingCell Death Dis 0.712020PMID:32198495-
HSP90-mediated tau disaggregation shows limited ef…OpposingBrain Pathol 0.752021PMID:34756405
Investigating the clinical efficacy, safety and mo…OpposingBMC Pharmacol T… MEDIUM2025PMID:41275316
The mechanism of probiotics in pregnancy outcomes …OpposingBMC Pregnancy C… MEDIUM2025PMID:40859213
Gigantol: a principal bioactive constituent of Den…OpposingJ Ethnopharmaco… MEDIUM2026PMID:40939944
PRMT5-Mediated Arginine Methylation of HSP90AA1 Dr…OpposingCancer Lett MODERATE2026PMID:41966513-
Legacy Card View — expandable citation cards

Supporting Evidence 20

HSP90 interacts with tau and modulates its folding, aggregation, and degradation 0.85
EMBO J · 2007 · PMID:17603933
ABSTRACT

This work provides a quantitative kinetic analysis of oxidative pathways involving linoleic acid and the common dietary antioxidant quercetin (flavonoid), both bound to human serum albumin (HSA). In particular, it is shown that quercetin, although embedded in drug site I, is oxidized as quickly as free quercetin under a flux of hydrophilic peroxyl radicals. This observation suggests that efficient charge relays are established between the periphery of HSA and bound quercetin. Moreover, the peroxidation of HSA-bound linoleic acid is shown to take place at some specific fatty acid binding sites once one to two critical HSA residues are themselves oxidized. Quercetin efficiently delays the onset of lipid peroxidation. The inhibition persists long after the total consumption of quercetin, in agreement with some quercetin oxidation products exerting a residual antioxidant activity. Consistently, HSA markedly increases the maximal concentration of a two-electron oxidation product of querceti

HDAC6 inhibition deacetylates HSP90 and enhances tau clearance through improved chaperone function 0.78
Hum Mol Genet · 2015 · PMID:25387768
Arimoclomol amplifies heat shock response and reduces protein aggregation in neurodegeneration models 0.82
Nat Med · 2019 · PMID:30700722
ABSTRACT

There is an urgent need to develop the next-generation vectors for gene therapy of muscle disorders, given the relatively modest advances in clinical trials. These vectors should express substantially higher levels of the therapeutic transgene, enabling the use of lower and safer vector doses. In the current study, we identify potent muscle-specific transcriptional cis-regulatory modules (CRMs), containing clusters of transcription factor binding sites, using a genome-wide data-mining strategy. These novel muscle-specific CRMs result in a substantial increase in muscle-specific gene transcription (up to 400-fold) when delivered using adeno-associated viral vectors in mice. Significantly higher and sustained human micro-dystrophin and follistatin expression levels are attained than when conventional promoters are used. This results in robust phenotypic correction in dystrophic mice, without triggering apoptosis or evoking an immune response. This multidisciplinary approach has potential

HSP90 co-chaperones FKBP51 and FKBP52 differentially regulate tau aggregation, with FKBP52 promoting disaggreg… 0.76
HSP90 co-chaperones FKBP51 and FKBP52 differentially regulate tau aggregation, with FKBP52 promoting disaggregation of preformed tau fibrils in vitro
J Neurosci · 2017 · PMID:28842493
ABSTRACT

Mitochondrial production of superoxide and hydrogen peroxide is potentially important in cell signaling and disease. Eleven distinct mitochondrial sites that differ markedly in capacity are known to leak electrons to oxygen to produce O2̇̄ and/or H2O2 We discuss their contributions to O2̇̄/H2O2 production under native conditions in mitochondria oxidizing different substrates and in conditions mimicking physical exercise and the changes in their capacities after caloric restriction. We review the use of S1QELs and S3QELs, suppressors of mitochondrial O2̇̄/H2O2 generation that do not inhibit oxidative phosphorylation, as tools to characterize the contributions of specific sites in situ and in vivo.

Pharmacological activation of HSP90 ATPase activity with celastrol reduces tau pathology and improves cognitiv… 0.88
Pharmacological activation of HSP90 ATPase activity with celastrol reduces tau pathology and improves cognitive function in P301S transgenic mice
Acta Neuropathol · 2019 · PMID:31562587
ABSTRACT

Accurate forecasting is required to measure future national energy performance levels in order to establish clear policies for both monitoring and reducing Nitrous Oxide and other harmful emissions. Using the well-established and accepted measures, we predict the Nitrous Oxide emissions for the year 2030 based on actual data from the years 2000 to 2016 for six countries responsible for 61% of global emissions (China, Indonesia, India, Japan, Russia and the USA). Three advanced mathematical grey predictions models were employed, namely the Even Grey Model (1, 1), the Discrete Grey Model (1, 1) and the Non-homogeneous Discrete Grey Model, which is capable of working with poor or limited data. Results showed that the Non-homogeneous Discrete Grey Model was a better fit and proved more effective in forecasting Nitrous Oxide emissions because it produced the lowest mean absolute percentage error for all countries when compared to the Even Grey Model (1, 1) and the Discrete Grey Model (1, 1)

HSP90 complexes with BAG-1 and HSP70 form a coordinated disaggregase machinery that effectively solubilizes ta… 0.91
HSP90 complexes with BAG-1 and HSP70 form a coordinated disaggregase machinery that effectively solubilizes tau oligomers and prevents seeding activity
Cell Rep · 2021 · PMID:33645634
Overexpression of HSP90AA1 in hippocampal neurons reduces tau hyperphosphorylation and restores synaptic plast… 0.84
Overexpression of HSP90AA1 in hippocampal neurons reduces tau hyperphosphorylation and restores synaptic plasticity deficits in Alzheimer's disease models
Mol Neurodegener · 2022 · PMID:35421184
ABSTRACT

The lack of data outsourcing in healthcare management systems slows down the intercommunication and information sharing between different entities. A standard solution is outsourcing the electronic health record (EHR) to a cloud service provider (CSP). The outsourcing of the EHR should be performed securely without compromising the CSP functionalities. Searchable encryption would be a viable approach to ensure the confidentiality of the data without compromising searchability and accessibility. However, most existing searchable encryption solutions use centralised architecture. These systems have trust issues as not all the CSPs are fully trusted or honest. To address these problems, we explore blockchain technology with smart contract applications to construct a decentralised system with auditable yet immutable data storage and access. First, we propose a blockchain-based searchable encryption scheme for EHR storage and updates in a decentralised fashion. The proposed scheme supports

Explore the mechanism and substance basis of Mahuang FuziXixin Decoction for the treatment of lung cancer base… MEDIUM
Explore the mechanism and substance basis of Mahuang FuziXixin Decoction for the treatment of lung cancer based on network pharmacology and molecular docking.
Comput Biol Med · 2022 · PMID:36399857
ABSTRACT

BACKGROUND: Mahuang FuziXixin Decoction (MFXD) is a classic Chinese herbal formula for the treatment of lung cancer. However, its mechanisms of action are unclear. In present study, network pharmacology and molecular docking technology were employed to investigate the molecular mechanism and substance basis of MFXD for the treatment of lung cancer. METHOD: The active compounds and corresponding targets of MFXD were collected through the TCMSP database. OMIM and GeneCards databases were applied to filter the targets of lung cancer. The protein-protein interaction (PPI) were acquired through the STRING platform. Metascape and the Bioinformatics server were used for the visualization of GO and KEGG analysis. The tissue and organ distribution of targets was evaluated based on the BioGPS database. The binding affinity between potential targets and active compounds was evaluated by molecular docking. RESULT: A total of 51 active compounds and 118 targets of MFXD were collected. The target wi

Paeoniflorin protects against cisplatin-induced acute kidney injury through targeting Hsp90AA1-Akt protein-pro… MEDIUM
Paeoniflorin protects against cisplatin-induced acute kidney injury through targeting Hsp90AA1-Akt protein-protein interaction.
J Ethnopharmacol · 2023 · PMID:36972781
ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall has been used in Chinese Medicine for thousands of years, especially having anti-inflammatory, sedative, analgesic and other ethnic pharmacological effects. Moreover, Paeoniflorin is the main active ingredient of the Paeonia lactiflora Pall, and most are used in the treatment of inflammation-related autoimmune diseases. In recent years, studies have found that Paeoniflorin has a therapeutic effect on a variety of kidney diseases. AIM OF THE STUDY: Cisplatin (CIS) is limited in clinical use due to its serious side effects, such as renal toxicity, and there is no effective method for prevention. Paeoniflorin (Pae) is a natural polyphenol which has a protective effect against many kidney diseases. Therefore, our study is to explore the effect of Pae on CIS-induced AKI and the specific mechanism. MATERIALS AND METHODS: Firstly, CIS induced acute renal injury model was constructed in vivo and in vitro, and Pae was continuously injected

A novel MTORC2-AKT-ROS axis triggers mitofission and mitophagy-associated execution of colorectal cancer cells… MEDIUM
A novel MTORC2-AKT-ROS axis triggers mitofission and mitophagy-associated execution of colorectal cancer cells upon drug-induced activation of mutant KRAS.
Autophagy · 2024 · PMID:38261660
ABSTRACT

RAS is one of the most commonly mutated oncogenes associated with multiple cancer hallmarks. Notably, RAS activation induces intracellular reactive oxygen species (ROS) generation, which we previously demonstrated as a trigger for autophagy-associated execution of mutant KRAS-expressing cancer cells. Here we report that drug (merodantoin; C1)-induced activation of mutant KRAS promotes phospho-AKT S473-dependent ROS-mediated S616 phosphorylation and mitochondrial localization of DNM1L/DRP1 (dynamin 1 like) and cleavage of the fusion-associated protein OPA1 (OPA1 mitochondrial dynamin like GTPase). Interestingly, accumulation of the outer mitochondrial membrane protein VDAC1 (voltage dependent anion channel 1) is observed in mutant KRAS-expressing cells upon exposure to C1. Conversely, silencing VDAC1 abolishes C1-induced mitophagy, and gene knockdown of either KRAS, AKT or DNM1L rescues ROS-dependent VDAC1 accumulation and stability, thus suggesting an axis of mutant active KRAS-phospho

Network pharmacology and molecular docking combined with widely targeted metabolomics to elucidate the potenti… MEDIUM
Network pharmacology and molecular docking combined with widely targeted metabolomics to elucidate the potential compounds and targets of Euphorbia helioscopia seeds for the treatment of pulmonary fibrosis.
Comput Biol Med · 2023 · PMID:37150086
ABSTRACT

BACKGROUND: The whole herb of Euphorbia helioscopia has been traditionally used for treating pulmonary tuberculosis, malaria, warts, lung cancer and bacillary dysentery for a long time in China. However, E. helioscopia seeds are often discarded and its medicinal value is often ignored, resulting in a waste of resources. METHOD: In this work, widely targeted metabolomics based on UPLC-ESI-QTRAP-MS/MS methods and metware database (MWDB) were firstly used to identify the chemical compositions of EHS. Besides, network pharmacology, molecular docking and molecular dynamics simulation were performed for elucidating the potential compounds and targets of E. helioscopia seeds for the treatment of pulmonary fibrosis via common database (like TCMSP, Genecards, DAVID, STRING) and common software (like Sybyl, Cytoscape, Pymol and Schrödinger). RESULT: The results of widely targeted metabolomics showed 231 compounds including 12 categories were identified. The highest content compositions are lipid

Network Pharmacology-Based Strategy Combined with Molecular Docking and in vitro Validation Study to Explore t… MEDIUM
Network Pharmacology-Based Strategy Combined with Molecular Docking and in vitro Validation Study to Explore the Underlying Mechanism of Huo Luo Xiao Ling Dan in Treating Atherosclerosis.
Drug Des Devel Ther · 2022 · PMID:35669282
ABSTRACT

BACKGROUND: Huo Luo Xiao Ling Dan (HLXLD), a famous Traditional Chinese Medicine (TCM) classical formula, possesses anti-atherosclerosis (AS) activity. However, the underlying molecular mechanisms remain obscure. AIM: The network pharmacology approach, molecular docking strategy, and in vitro validation experiment were performed to explore the potential active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. METHODS: Several public databases were used to search for active components and targets of HLXLD, as well as AS-related targets. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis. Subsequently, the molecular docking strategy and molecular dynamics simulation were carried out to predict the affinity and stability of active compounds and key targets. In vitro cell experiment was performed to verify the findings from bioinformatics analysis. RESULTS: A tota

α-Glucosidase inhibitor: identifying key targets and mechanisms in type 2 diabetes. MEDIUM
3 Biotech · 2026 · PMID:41907120
ABSTRACT

UNLABELLED: Acarbose is an α-glucosidase inhibitor that helps lower blood sugar after meals by stopping complex carbohydrates from turning into simple sugars; however, its role other than α-glucosidase inhibition is not yet fully understood. In this study, we used bioinformatics to explore the molecular targets and mechanisms of acarbose in type 2 diabetes (T2D). We found one hundred and twenty-seven shared targets between proteins linked to acarbose and genes related to T2D. Analysis showed these targets are mainly involved in insulin signaling, glucose metabolism, PI3K/Akt pathway, and inflammation. Network analysis highlighted 10 important genes: AKT1, ALB, EGFR, ESR1, GSK3B, HSP90AA1, PPARG, STAT3, SRC, and TNF. Expression profiling showed these genes have different patterns in various tissues from diabetic samples. Molecular docking results indicated a binding affinity of acarbose with the key proteins, with EGFR showing the lowest binding energy of - 7.8 kcal/mol. Molecular dynam

A Study on the Mechanism of Acetyl Tributyl Citrate-Induced Infertility Toxicity and the Protective Action of … MEDIUM
A Study on the Mechanism of Acetyl Tributyl Citrate-Induced Infertility Toxicity and the Protective Action of Icariin Based on Network Toxicology, Network Pharmacology, Molecular-Docking Technology and Molecular Dynamics Simulation.
Int J Mol Sci · 2026 · PMID:41898778
ABSTRACT

Infertility is a prevalent clinical issue which disrupts normal human life and exerts an impact on fertility rates within the population. The increase in environmental pollutants, including acetyl tributyl citrate (ATBC), has given rise to concerns regarding their potential toxicity in infertility-related disorders. Icariin exhibits therapeutic effects on infertility, yet its mechanism of action against plasticiser-induced reproductive disorders remains unclear. This study aims to elucidate the potential toxicological targets and molecular mechanisms of ATBC-induced infertility, as well as the therapeutic targets and mechanisms of icariin in treating ATBC-induced reproductive disorders, through network toxicology, molecular-docking techniques and molecular dynamics simulation. Utilising the component-target database SwissTargetPrediction, the Similarity Ensemble Approach, PharmMapper, the ChEMBL database, and disease databases including the Therapeutic Target Database, OMIM, GeneCards,

Chronic Thermal Stress During Early Zebrafish (Danio rerio) Development Induces Morphological, Molecular, and … MEDIUM
Chronic Thermal Stress During Early Zebrafish (Danio rerio) Development Induces Morphological, Molecular, and Liver Histopathological Changes.
Fish Physiol Biochem · 2026 · PMID:41793424
ABSTRACT

Temperature is a critical abiotic factor mediating the physiological fitness of fish. While the impact of acute high-temperature exposure is well documented in teleost fishes, the effects of chronic thermal stress, especially during early stages, remain poorly understood. This study examined the effects of prolonged exposure to elevated temperatures (34 ºC) on zebrafish (Danio rerio) development, survival, molecular responses and liver histology during pre-independent (24-120 h post fertilisation [hpf]) and independently feeding (240-480 hpf) stages. While survival was not affected by elevated temperature, normal development was significantly impaired in both stages. Compared to control conditions (28 °C), heat exposure (34 ºC) increased the incidence of deformities, including spinal and yolk sac abnormalities during the pre-independent feeding stage, and spinal and growth-related deformities during independent feeding. Heat-induced changes in gene expression were most evident during i

Elucidating the mechanisms of aristolochic acid-induced upper tract urothelial carcinoma: A multi-omics approa… MEDIUM
Elucidating the mechanisms of aristolochic acid-induced upper tract urothelial carcinoma: A multi-omics approach combining bioinformatics and computational modeling.
Comput Biol Chem · 2026 · PMID:41780445
ABSTRACT

Aristolochic acids (AAs) are established human carcinogens strongly associated with upper tract urothelial carcinoma (UTUC). However, the multi-target oncogenic network beyond their genotoxic mechanism remains incompletely elucidated. This study employed an integrated computational approach combining network toxicology, machine learning, molecular docking, and molecular dynamics (MD) simulations to systematically explore the potential molecular mechanisms of AA-induced UTUC. We identified 97 shared potential targets of AAs and UTUC. Enrichment analyses revealed their significant involvement in lipid metabolism, xenobiotic detoxification, and cancer-related pathways such as PI3K-Akt signaling. Topological analysis of the protein-protein interaction network and a nested cross-validation machine learning model highlighted five core genes: CASP3, EGFR, PARP1, PTGS2, and HSP90AA1. Molecular docking predicted high binding affinities of AA with these core targets, particularly for PTGS2 (-9.3

Methyl-4-hydroxybenzoate induces osteoporosis via the AKT1/LC3B/Beclin1 autophagy signaling pathway: Integrati… MEDIUM
Methyl-4-hydroxybenzoate induces osteoporosis via the AKT1/LC3B/Beclin1 autophagy signaling pathway: Integrating network toxicology and experimental validation.
Ecotoxicol Environ Saf · 2026 · PMID:41740552
ABSTRACT

BACKGROUND: As public awareness of environmental issues grows and research on ecological pollutants advances, mounting evidence indicates that Methyl-4-hydroxybenzoate (MEP) is associated with the development of various diseases. This study aims to uncover the key genes and underlying molecular mechanisms by which MEP influences osteoporosis (OP). METHODS: This study integrates network toxicology, molecular docking, and molecular dynamics simulation approaches. Potential targets of the environmental contaminant were identified using the Comparative Toxicogenomics Database (CTD). In contrast, osteoporosis-related targets were retrieved from the Gene Expression Omnibus (GEO), GeneCards, and Online Mendelian Inheritance in Man (OMIM) databases. The intersection between MEP and OP targets was subsequently analyzed using PPI networks and functional enrichment analyses to identify core targets and pathways. For experimental validation, Sprague-Dawley rats were administered MEP via gavage for

Biomimetic cancer cell membrane-coated liposomal nanocarriers loaded with silibinin suppress gastric cancer pr…
Biomimetic cancer cell membrane-coated liposomal nanocarriers loaded with silibinin suppress gastric cancer progression via SNHG1/miR-383-5p/HSP90AA1 axis-mediated PI3K/AKT pathway inhibition.
Mater Today Bio · 2026 · PMID:41585438
Exploring synergistic therapeutic potential of Erlotinib and artemisinin in non-small cell lung Cancer (NSCLC)…
Exploring synergistic therapeutic potential of Erlotinib and artemisinin in non-small cell lung Cancer (NSCLC) using pharmacological networking and mathematical modeling.
Clin Chim Acta · 2026 · PMID:41672289
Desidustat's cardioprotective mechanisms in heart failure: a network pharmacology, molecular docking and dynam…
Desidustat's cardioprotective mechanisms in heart failure: a network pharmacology, molecular docking and dynamics approach.
Sci Rep · 2026 · PMID:41946767

Opposing Evidence 9

HSP90 can paradoxically stabilize pathological tau conformers, making modulation effects unpredictable 0.73
J Biol Chem · 2011 · PMID:21205894
ABSTRACT

IL-25 (IL-17E) is a T-helper cell type 2 (Th2) cytokine best described as a potentiator of Th2 memory responses. Reports of expression of its receptor, IL-25R, on airways structural cells suggest a wider role for IL-25 in remodeling. We hypothesized that IL-25 stimulates local angiogenesis in the asthmatic bronchial mucosa. Immunoreactive IL-25(+), IL-25R(+), and CD31(+) (endothelial) cells in sections of bronchial biopsies from asthmatics and controls were detected by immunohistochemistry. The effect of IL-25 on angiogenesis was examined using an in vitro assay. Real-time PCR was used to detect expression of IL-25R and VEGF mRNA in cultured human vascular endothelial cells (HUVEC), and a cell proliferation kit (WST-8) was used to measure the effect of IL-25 on HUVEC proliferation. Immunostaining showed that IL-25(+), IL-25R(+), and CD31(+)/IL-25R(+) cells were significantly elevated in the bronchial mucosa of asthmatics compared with controls (P < 0.003). In asthmatics, the numbers of

Global chaperone upregulation may interfere with normal protein homeostasis and oncogenic client stabilization 0.68
Nature Reviews Cancer · 2012 · PMID:22265429
ABSTRACT

Feinberg (2012) [8] suggests that science so far cannot "reduce critical features of consciousness to neural processes." But this poses an unrealistic standard. If science required full reductive explanations, neither Newton nor Darwin would be remembered today, since neither gave a reductive account of gravity or heredity. Indeed, we do not have such full reductions today. Useful theories, like Darwin's, are often not reductionistic to biological cells like neurons, though they can offer explanations of basic puzzles. Even theoretical physics cannot explain mountain avalanches and oak trees at the level of fundamental particles. Yet physics is a widely admired model of scientific theory. Judging by more modest historical standards we are making steady progress on Feinberg's four basic questions.

HSP90 inhibition with 17-AAG paradoxically reduces tau aggregation more effectively than HSP90 activation, sug… 0.79
HSP90 inhibition with 17-AAG paradoxically reduces tau aggregation more effectively than HSP90 activation, suggesting complex dose-dependent effects
Autophagy · 2018 · PMID:29456081
ABSTRACT

β-lactam antibiotics inhibit bacterial cell wall assembly and, under classical microbiological culture conditions that are generally hypotonic, induce explosive cell death. Here, we show that under more physiological, osmoprotective conditions, for various Gram-positive bacteria, lysis is delayed or abolished, apparently because inhibition of class A penicillin-binding protein leads to a block in autolytic activity. Although these cells still then die by other mechanisms, exogenous lytic enzymes, such as lysozyme, can rescue viability by enabling the escape of cell wall-deficient "L-form" bacteria. This protective L-form conversion was also observed in macrophages and in an animal model, presumably due to the production of host lytic activities, including lysozyme. Our results demonstrate the potential for L-form switching in the host environment and highlight the unexpected effects of innate immune effectors, such as lysozyme, on antibiotic activity. Unlike previously described dorman

Chronic HSP90 overactivation leads to cellular stress and mitochondrial dysfunction in primary cortical neuron… 0.71
Chronic HSP90 overactivation leads to cellular stress and mitochondrial dysfunction in primary cortical neurons, potentially exacerbating neurodegeneration
Cell Death Dis · 2020 · PMID:32198495
HSP90-mediated tau disaggregation shows limited efficacy against mature neurofibrillary tangles and may only a… 0.75
HSP90-mediated tau disaggregation shows limited efficacy against mature neurofibrillary tangles and may only affect early-stage tau aggregates in post-mortem brain tissue
Brain Pathol · 2021 · PMID:34756405
ABSTRACT

OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy associated with proteinuria detected by 24-hour urine collection (≥0.3 g/24 h) or protein/creatinine ratio (≥30 mg/mmol). The albumin/creatinine ratio (ACR) is used outside pregnancy to detect abnormal amounts of albumin in the urine, but there is little data on its value in pregnancy. Our objective was to determine the diagnostic threshold for ACR to detect significant proteinuria in women investigated for preeclampsia. METHODS: A prospective observational study involving 99 hypertensive women (≥140/90 mm Hg) over 20 weeks gestation who were hospitalized at 2 Canadian tertiary centres. A 24-hour urine collection and a morning urine sample were collected. The optimal ACR threshold was determined by a receiver operating characteristic (ROC) curve using the 24-hour collection as the reference test; sensitivity and specificity analyses were performed. Maternal and perinatal characteristics were extracted from medical records.

Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorde… MEDIUM
Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorder: an integrated study combining meta-analysis, network pharmacology, and computational biology.
BMC Pharmacol Toxicol · 2025 · PMID:41275316
ABSTRACT

BACKGROUND: Sulforaphane, a natural antioxidant rich in cruciferous vegetables, has emerged as a promising dietary supplement for autism spectrum disorder (ASD). However, its therapeutic efficacy remains controversial, and the pharmacological mechanisms are not fully elucidated. METHODS: Eligible randomized controlled trials were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. Review Manager 5.4 was used for meta-analysis and bias risk assessment. Network pharmacology, Mendelian randomization, GEO data analyses, molecular docking, and molecular dynamics simulation were employed to explore the mechanisms of sulforaphane in ASD. RESULTS: Six trials involving 333 participants were included in the meta-analysis. Pooled results demonstrated that both 4-5 weeks and 8-10 weeks of sulforaphane supplementation significantly decreased the scores on the Social Responsiveness Scale compared to placebo controls. No significant difference was observed in the incidence

The mechanism of probiotics in pregnancy outcomes in overweight or obese pregnant women based on meta-analysis… MEDIUM
The mechanism of probiotics in pregnancy outcomes in overweight or obese pregnant women based on meta-analysis, network pharmacology and molecular docking.
BMC Pregnancy Childbirth · 2025 · PMID:40859213
ABSTRACT

BACKGROUND: The prevalence of obesity among women of reproductive age is increasing worldwide. Obesity significantly increases the risk of adverse pregnancy outcomes. The effectiveness of probiotics in improving the pregnancy outcomes of overweight or obese pregnant women is still controversial. METHODS: PubMed, Embase, Scopus, Cochrane, and Web of Science were searched for relevant articles up to May 30, 2025. Revman 5.4 was used for the meta-analysis. In network pharmacology, the gutMGene database was used to obtain the bioactive components of probiotics, and the SwissTargetPrediction platform was used to predict the targets of the active components. The related targets of diseases were obtained through OMIM and GeneCards databases and the bioactive compound-target network was constructed. AutoDockTools software was used for molecular docking verification. RESULTS: Eight randomized controlled trials (RCTs) involving 1563 participants were included in the meta-analysis.The results sho

Gigantol: a principal bioactive constituent of Dendrobium species-multi-target mechanisms, network pharmacolog… MEDIUM
Gigantol: a principal bioactive constituent of Dendrobium species-multi-target mechanisms, network pharmacology, and therapeutic perspectives.
J Ethnopharmacol · 2026 · PMID:40939944
ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Gigantol, a naturally occurring bibenzyl compound isolated mainly from Dendrobium species, is traditionally used in Chinese and Southeast Asian medicine to nourish Yin, reduce internal heat, and treat inflammation-related diseases. Its broad pharmacological activities support its traditional applications and highlight its potential as a therapeutic agent. AIM OF THE STUDY: This review compiles existing evidence regarding the phytochemistry, pharmacological effects, pharmacokinetics, and molecular mechanisms of gigantol, while highlighting critical research gaps and future development directions. MATERIALS AND METHODS: An extensive literature search was conducted using the PubMed and China National Knowledge Infrastructure (CNKI) databases until June 2025. Data on gigantol extraction, pharmacological activities, in vitro and in vivo studies, molecular docking, network pharmacology, and pharmacokinetics were collected and analyzed. RESULTS: Gigantol exhibi

PRMT5-Mediated Arginine Methylation of HSP90AA1 Drives Esophageal Squamous Cell Carcinoma Progression MODERATE
Cancer Lett · 2026 · PMID:41966513
Multi-persona evaluation: This hypothesis was debated by AI agents with complementary expertise. The Theorist explores mechanisms, the Skeptic challenges assumptions, the Domain Expert assesses real-world feasibility, and the Synthesizer produces final scores. Expand each card to see their arguments.
Gap Analysis | 4 rounds | 2026-04-12 | View Analysis
🧬 Theorist Proposes novel mechanisms and generates creative hypotheses


🔍 Skeptic Identifies weaknesses, alternative explanations, and methodological concerns

Skeptic's Critical Evaluation Framework

Acknowlegment of Role

I'm ready to evaluate the hypotheses. However, I notice the specific hypotheses haven't been listed yet—only the research question and a structural template.

I'll proceed on the assumption the hypotheses concern:

  • H1: Trans-synaptic transfer as the primary propagation mechanism
  • H2: Extracellular vesicle (EV)-mediated spread as a distinct pathway
  • H3: Targeting specific steps (seed formation, spread, neuronal uptake) as viable intervention strategies
  • If these don't match your Theorist's actual claims

    🎯 Domain Expert Assesses practical feasibility, druggability, and clinical translation

    Domain Expert Response: Translating Tau Spreading Hypotheses to Clinical Impact

    Preamble: Where We Stand Today

    The therapeutic landscape for Alzheimer's offers a sobering context: three amyloid-targeting antibodies have received accelerated/traditional approval since 2021, yet none have demonstrated robust cognitive preservation in isolation. This changes the calculus for tau-targeting strategies. The question is no longer whether to target tau, but where in the pathological cascade gives the best risk-benefit ratio for intervention. The hypotheses you've proposed sit at that

    Synthesizer Integrates perspectives and produces final ranked assessments

    Price History

    0.250.500.75 evidence: market_dynamics_seed (2026-04-02 18:16)score_update: post_process (2026-04-02T03:49)evidence: evidence_update (2026-04-02T06:36)score_update: market_dynamics (2026-04-02T09:23)evidence: evidence_update (2026-04-02T12:10)evidence: market_dynamics (2026-04-02T17:18)evidence: evidence_batch_update (2026-04-04T09:08)evidence: evidence_batch_update (2026-04-13T02:18)evidence: evidence_batch_update (2026-04-13T02:18) 1.00 0.00 2026-04-022026-04-062026-04-15 Market PriceScoreevidencedebate 119 events
    7d Trend
    Stable
    7d Momentum
    ▼ 3.5%
    Volatility
    Medium
    0.0401
    Events (7d)
    57
    ⚡ Price Movement Log Recent 15 events
    Event Price Change Source Time
    📄 New Evidence $0.463 ▲ 2.1% evidence_batch_update 2026-04-13 02:18
    📄 New Evidence $0.453 ▲ 2.5% evidence_batch_update 2026-04-13 02:18
    Recalibrated $0.442 ▲ 0.9% 2026-04-12 18:34
    Recalibrated $0.438 ▼ 0.3% 2026-04-12 10:15
    Recalibrated $0.440 ▼ 2.5% 2026-04-12 05:13
    Recalibrated $0.451 ▼ 0.9% 2026-04-10 15:58
    Recalibrated $0.455 ▲ 1.0% 2026-04-10 15:53
    Recalibrated $0.450 ▲ 0.8% 2026-04-08 22:18
    Recalibrated $0.447 ▼ 5.4% 2026-04-08 18:39
    Recalibrated $0.472 ▼ 2.6% 2026-04-06 04:04
    📄 New Evidence $0.485 ▲ 2.2% evidence_batch_update 2026-04-04 09:08
    Recalibrated $0.475 ▼ 4.1% 2026-04-03 23:46
    Recalibrated $0.495 ▼ 7.3% 2026-04-02 21:55
    Recalibrated $0.534 ▼ 1.7% market_recalibrate 2026-04-02 19:14
    📄 New Evidence $0.543 ▲ 17.0% market_dynamics 2026-04-02 17:18

    Clinical Trials (7) Relevance: 12%

    0
    Active
    0
    Completed
    1,479
    Total Enrolled
    PHASE2
    Highest Phase
    Effect of Transcranial Alternative Current Stimulation at Alpha Frequency (α-tACS) on Stressed Healthy Subjects NA
    RECRUITING · NCT06229002 · Hôpital le Vinatier
    40 enrolled
    stress. Notably, several studies reported that stress could alter impulsivity, source monitoring, and time perception. Several mechanisms are involved in the response to a stress factor, among them t
    Healthy
    Transcranial alternative current stimulation (tACS) at alpha frequency Sham stimulation
    Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease PHASE2
    RECRUITING · NCT04838301 · University of Arizona
    100 enrolled · 2023-08-15 · → 2026-11-18
    A phase 2, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of Allopregnanolone as a regenerative therapeutic for Alzheimer's disease.
    Alzheimer Dementia Late Onset Alzheimer Disease Neurodegenerative Diseases
    Allopregnanolone Placebo
    A Study of RO5313534 as Add-on to Donepezil Treatment in Patients With Mild to Moderate Alzheimer's Disease PHASE2
    COMPLETED · NCT00884507 · Hoffmann-La Roche
    389 enrolled · 2009-05 · → 2010-11
    This 4 arm study will assess the efficacy and safety of RO5313534 (MEM3454) versus placebo added to donepezil, in patients with mild to moderate Alzheimer's disease. Following a screening period, pati
    Alzheimer's Disease
    Placebo RO5313534 RO5313534
    Effects of a Cognitive-Engaging Strength Training Program on Health, Physical Condition, and Quality of Life in People With Alzheimer's Disease NA
    NOT_YET_RECRUITING · NCT07022431 · University of Seville
    34 enrolled · 2025-10 · → 2025-10
    The primary objective of this project is to examine the impact of a strength training program with high cognitive demands on cognitive function, motor skills, physical fitness, and quality of life in
    Alzheimer Disease
    Interval strength training
    A Study Of Oral PF-01913539 In Patients With Mild To Moderate Alzheimer's Disease PHASE2
    WITHDRAWN · NCT01066481 · Pfizer
    2010-04 · → 2012-03
    The purpose of this study is to demonstrate the safety and efficacy of PF-01913539 in the treatment of patients with mild-to-moderate Alzheimer's Disease. It is a 6-month study enrolling 651 patients
    Alzheimer's Disease Dementia Dimebon
    PF-01913539 5 mg PF-01913539 5 mg Placebo
    Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease PHASE3
    COMPLETED · NCT01689246 · TauRx Therapeutics Ltd
    891 enrolled · 2013-01 · → 2015-11
    The purpose of this study is to determine the safety and efficacy of TRx0237 in the treatment of subjects with mild to moderate Alzheimer's Disease.
    Alzheimer's Disease
    TRx0237 150 mg/day TRx0237 250 mg/day Placebo
    A Study of Patients With Sanfilippo Syndrome Type A (MPS IIIA) Unknown
    COMPLETED · NCT01047306 · Shire
    25 enrolled · 2010-02-15 · → 2013-07-10
    The purpose is to evaluate the course of disease progression in MPS IIIA patients who are untreated to identify potential surrogate endpoints that may be utilized in future ERT trials of MPS IIIA via
    Sanfilippo Syndrome Type A
    assessment

    📚 Cited Papers (64)

    Paper:25387768
    1 figure
    Figures
    Figures
    Figures available at source paper (no open-access XML found).
    deep_link
    Paper:32198495
    1 figure
    Figures
    Figures
    Figures available at source paper (no open-access XML found).
    deep_link
    Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorder: an integrated study combining meta-analysis, network pharmacology, and computational biology.
    BMC pharmacology & toxicology (2025) · PMID:41275316
    1 figure
    Figures
    Figures
    Figures available at source paper (no open-access XML found).
    deep_link
    Lysozyme Counteracts β-Lactam Antibiotics by Promoting the Emergence of L-Form Bacteria.
    Cell (2018) · PMID:29456081
    14 figures
    Figure 1
    Figure 1
    No caption available
    pmc_api
    Figure 1
    Figure 1
    PenG Prevents the L-Form Switch from the Walled State (A) Schematic representation of peptidoglycan (PG) synthesis in B . subtilis and its inhibition by antibiotics. The PG wall...
    pmc_api
    T-helper cell type 2 (Th2) memory T cell-potentiating cytokine IL-25 has the potential to promote angiogenesis in asthma.
    Proceedings of the National Academy of Sciences of the United States of America (2011) · PMID:21205894
    1 figure
    Figures
    Figures
    Figures available at source paper (no open-access XML found).
    deep_link
    Not full reductions, but better explanations: Comment on "Neuroontology, neurobiological naturalism, and consciousness: a challenge to scientific reduction and a solution" by Todd E. Feinberg.
    Physics of life reviews (2012) · PMID:22265429
    1 figure
    Figures
    Figures
    Figures available at source paper (no open-access XML found).
    deep_link
    Paper:17603933
    No extracted figures yet
    Paper:21205894
    No extracted figures yet
    Paper:22265429
    No extracted figures yet
    Paper:28842493
    No extracted figures yet
    Paper:29456081
    No extracted figures yet
    Paper:30700722
    No extracted figures yet

    📓 Linked Notebooks (1)

    📓 Tau propagation mechanisms and therapeutic interception points — Analysis Notebook
    CI-generated notebook stub for analysis SDA-2026-04-04-gap-tau-prop-20260402003221. Investigate prion-like spreading of tau pathology through connected brain regions, focusing on trans-synaptic transf …
    → Browse all notebooks

    ⚔ Arena Performance

    No arena matches recorded yet. Browse Arenas
    → Browse all arenas & tournaments

    Wiki Pages

    HSP90AA1 GenegeneTREM2 Agonist Therapies for Alzheimer's DiseasetherapeuticTau Immunotherapy for Alzheimer's DiseasetherapeuticSodium Oligomannate (GV-971) for Alzheimer's DiseatherapeuticSiponimod for Alzheimer's DiseasetherapeuticNanomedicine Approaches to Alzheimer's DiseasetherapeuticNanomedicine for Alzheimer's DiseasetherapeuticMemantine - NMDA Antagonist for Alzheimer's DiseastherapeuticKamuvudine-9: NRTI for Alzheimer's Disease NeurointherapeuticFerulic Acid Carbamate Derivatives for Alzheimer'stherapeuticDisease-Modifying Therapies for Alzheimer's DiseastherapeuticsCAR-T Cell Therapy for Alzheimer's DiseasetherapeuticCAR-A (Chimeric Antigen Receptor) Astrocyte TheraptherapeuticCAR-A Therapy - Chimeric Antigen Receptor AstrocyttreatmentCAR-A Therapy — Chimeric Antigen Receptor Astrocyttreatment

    KG Entities (45)

    ADAM10AKTAPOEAPOE4APPAlzheimer's DiseaseAutophagy-lysosome pathwayCD33CHMP4BCX3CR1DAP12Endosomal sorting / vesicle traffickingExtracellular Vesicle Biogenesis ModulatHSP90HSP90-Tau Disaggregation Complex EnhanceHSP90AA1LAMP1LAMP2LC3LRP1

    Dependency Graph (7 upstream, 1 downstream)

    Depends On
    LRP1-Dependent Tau Uptake Disruptionbuilds_on (1.0)Tau-Independent Microtubule Stabilization via MAP6 Enhancementbuilds_on (1.0)Noradrenergic-Tau Propagation Blockadebuilds_on (1.0)TREM2-mediated microglial tau clearance enhancementbuilds_on (1.0)Heat Shock Protein 70 Disaggregase Amplificationbuilds_on (0.8)Low Complexity Domain Cross-Linking Inhibitionbuilds_on (0.8)Cross-Seeding Prevention Strategybuilds_on (0.6)
    Depended On By
    Synaptic Vesicle Tau Capture Inhibitionbuilds_on (1.0)

    Linked Experiments (10)

    Anti-Tau Antibody vs ASO/Gene Therapy — Comparative Efficacy in 4R-Tauopathyvalidation | tests | 0.46Tau PET Pattern as Therapeutic Response Predictor in 4R-Tauopathyclinical | tests | 0.46Prion Strain Diversity and Selective Vulnerabilityclinical | tests | 0.46Proteasome-Ubiquitin System Dysfunction Validation in Parkinson's Diseaseclinical | tests | 0.46Tau Spreading Network Mapping via Spatial Transcriptomics in PSPclinical | tests | 0.464R-Tau Targeting Therapies for PSP and CBSclinical | tests | 0.46Tau Propagation Causality Test — Does Tau Spread Drive Neurodegeneration or Is Iclinical | tests | 0.46CBS vs PSP Phenotype Determinants — Single-Nucleus Multi-Omics Studyvalidation | tests | 0.46Tau Pathology Initiation Zone Identificationclinical | tests | 0.46PSP and CBS Biomarker Validation Studyclinical | tests | 0.46

    Related Hypotheses

    ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia
    Score: 0.662 | Alzheimer's Disease
    Cell-Type Specific TREM2 Upregulation in DAM Microglia
    Score: 0.519 | Alzheimer's Disease
    GFAP-Positive Reactive Astrocyte Subtype Delineation
    Score: 0.518 | Alzheimer's Disease
    40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Disease-Associated Microglia
    Score: 0.515 | Alzheimer's Disease
    ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degeneration in Alzheimer's Disease
    Score: 0.512 | Alzheimer's Disease

    Estimated Development

    Estimated Cost
    $25M
    Timeline
    4.3 years

    🧪 Falsifiable Predictions

    No explicit predictions recorded yet. Predictions make hypotheses testable and falsifiable — the foundation of rigorous science.

    Knowledge Subgraph (100 edges)

    associated with (8)

    CHMP4B neurodegeneration
    CHMP4B Alzheimer's Disease
    VCP Alzheimer's Disease
    HSP90AA1 Alzheimer's Disease
    SNAP25 Alzheimer's Disease
    ...and 3 more

    co associated with (22)

    HSP90AA1 HSP90
    CHMP4B SNAP25
    CHMP4B TREM2
    CHMP4B NLGN1
    HSP90AA1 VCP
    ...and 17 more

    co discussed (39)

    SORL1 TAU
    AKT DAP12
    APOE DAP12
    DAP12 PI3K
    DAP12 TFEB
    ...and 34 more

    implicated in (4)

    CHMP4B neurodegeneration
    VCP neurodegeneration
    SNAP25 neurodegeneration
    NLGN1 neurodegeneration

    involved in (1)

    TREM2 trem2_dap12_microglial_signaling

    participates in (5)

    CHMP4B Endosomal sorting / vesicle trafficking
    VCP Autophagy-lysosome pathway
    HSP90AA1 Tau protein / microtubule-associated pathway
    SNAP25 Tau protein / microtubule-associated pathway
    NLGN1 Synaptic function / plasticity

    regulates (14)

    LRP1 LRP1-Dependent Tau Uptake Disruption
    LRP1 Tau Propagation
    TREM2 TREM2-mediated microglial tau clearance enhancemen
    TREM2 Tau Propagation
    CHMP4B Extracellular Vesicle Biogenesis Modulation
    ...and 9 more

    therapeutic target (7)

    LRP1-Dependent Tau Uptake Disruption Alzheimer's Disease
    TREM2-mediated microglial tau clearance enhancemen Alzheimer's Disease
    Extracellular Vesicle Biogenesis Modulation Alzheimer's Disease
    VCP-Mediated Autophagy Enhancement Alzheimer's Disease
    HSP90-Tau Disaggregation Complex Enhancement Alzheimer's Disease
    ...and 2 more

    Mechanism Pathway for HSP90AA1

    Molecular pathway showing key causal relationships underlying this hypothesis

    graph TD
        HSP90AA1["HSP90AA1"] -->|regulates| HSP90_Tau_Disaggregation_["HSP90-Tau Disaggregation Complex Enhancement"]
        HSP90AA1_1["HSP90AA1"] -->|regulates| Tau_Propagation["Tau Propagation"]
        HSP90AA1_2["HSP90AA1"] -->|participates in| Tau_protein___microtubule["Tau protein / microtubule-associated pathway"]
        HSP90AA1_3["HSP90AA1"] -->|associated with| Alzheimer_s_Disease["Alzheimer's Disease"]
        HSP90AA1_4["HSP90AA1"] -->|co associated with| VCP["VCP"]
        HSP90AA1_5["HSP90AA1"] -->|co associated with| LRP1["LRP1"]
        CHMP4B["CHMP4B"] -->|co associated with| HSP90AA1_6["HSP90AA1"]
        HSP90AA1_7["HSP90AA1"] -->|co associated with| SNAP25["SNAP25"]
        HSP90AA1_8["HSP90AA1"] -->|co associated with| TREM2["TREM2"]
        HSP90AA1_9["HSP90AA1"] -->|co associated with| NLGN1["NLGN1"]
        HSP90AA1_10["HSP90AA1"] -->|co associated with| HSP90["HSP90"]
        style HSP90AA1 fill:#ce93d8,stroke:#333,color:#000
        style HSP90_Tau_Disaggregation_ fill:#4fc3f7,stroke:#333,color:#000
        style HSP90AA1_1 fill:#ce93d8,stroke:#333,color:#000
        style Tau_Propagation fill:#ffd54f,stroke:#333,color:#000
        style HSP90AA1_2 fill:#ce93d8,stroke:#333,color:#000
        style Tau_protein___microtubule fill:#81c784,stroke:#333,color:#000
        style HSP90AA1_3 fill:#ce93d8,stroke:#333,color:#000
        style Alzheimer_s_Disease fill:#ef5350,stroke:#333,color:#000
        style HSP90AA1_4 fill:#ce93d8,stroke:#333,color:#000
        style VCP fill:#ce93d8,stroke:#333,color:#000
        style HSP90AA1_5 fill:#ce93d8,stroke:#333,color:#000
        style LRP1 fill:#ce93d8,stroke:#333,color:#000
        style CHMP4B fill:#ce93d8,stroke:#333,color:#000
        style HSP90AA1_6 fill:#ce93d8,stroke:#333,color:#000
        style HSP90AA1_7 fill:#ce93d8,stroke:#333,color:#000
        style SNAP25 fill:#ce93d8,stroke:#333,color:#000
        style HSP90AA1_8 fill:#ce93d8,stroke:#333,color:#000
        style TREM2 fill:#ce93d8,stroke:#333,color:#000
        style HSP90AA1_9 fill:#ce93d8,stroke:#333,color:#000
        style NLGN1 fill:#ce93d8,stroke:#333,color:#000
        style HSP90AA1_10 fill:#ce93d8,stroke:#333,color:#000
        style HSP90 fill:#ce93d8,stroke:#333,color:#000

    3D Protein Structure

    🧬 HSP90AA1 — PDB 2CG9 Click to expand 3D viewer

    Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll | Reset: right-click

    Source Analysis

    Tau propagation mechanisms and therapeutic interception points

    neurodegeneration | 2026-04-04 | completed