Digital Twin-Guided Metabolic Reprogramming
Quality Report Card click to collapse
From Analysis:
Digital biomarkers and AI-driven early detection of neurodegeneration
Can speech, gait, retinal imaging, sleep, and smartphone data detect neurodegeneration 5-10 years before diagnosis?
Hypotheses from Same Analysis (6)
These hypotheses emerged from the same multi-agent debate that produced this hypothesis.
Description
Molecular Mechanism and Rationale
The digital twin-guided metabolic reprogramming approach targets the fundamental bioenergetic dysfunction underlying neurodegenerative diseases through precise modulation of the PGC-1α (PPARGC1A) and AMPK α1 (PRKAA1) signaling axis. PGC-1α serves as the master regulator of mitochondrial biogenesis and oxidative metabolism, orchestrating the transcription of nuclear respiratory factors NRF1 and NRF2, which subsequently activate mitochondrial transcription factor A (TFAM) to promote mitochondrial DNA replication and respiratory chain assembly. In neurodegenerative conditions, PGC-1α expression becomes progressively dysregulated, leading to impaired mitochondrial function, reduced ATP synthesis, and accumulation of reactive oxygen species.
Figures & Visualizations
3D Protein Structure
Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.
Dimension Scores
Legacy Card View — expandable citation cards
✓ Supporting Evidence 13
OBJECTIVE: We performed a systematic review to identify which genetic variants predict response to diabetes medications. RESEARCH DESIGN AND METHODS: We performed a search of electronic databases (PubMed, EMBASE, and Cochrane Database) and a manual search to identify original, longitudinal studies of the effect of diabetes medications on incident diabetes, HbA1c, fasting glucose, and postprandial glucose in prediabetes or type 2 diabetes by genetic variation. Two investigators reviewed titles, abstracts, and articles independently. Two investigators abstracted data sequentially and evaluated study quality independently. Quality evaluations were based on the Strengthening the Reporting of Genetic Association Studies guidelines and Human Genome Epidemiology Network guidance. RESULTS: Of 7,279 citations, we included 34 articles (N = 10,407) evaluating metformin (n = 14), sulfonylureas (n = 4), repaglinide (n = 8), pioglitazone (n = 3), rosiglitazone (n = 4), and acarbose (n = 4). Studies
Metformin restores mitochondrial bioenergetics and redox homeostasis through modulation of mitochondrial bioge… MEDIUM▼
Molybdenum cofactor deficiency (MoCD) is an inborn error of sulfur metabolism caused by inactivating variants in the genes encoding enzymes of the molybdenum cofactor biosynthetic pathway. Patients present with accumulation of sulfite in the brain with secondary mitochondrial bioenergetics and severe neurological manifestations. To investigate the pathophysiology of this disorder, we evaluated mitochondrial and redox homeostasis in fibroblasts derived from a patient with MoCD type A (MOCS1 deficiency) and in an animal model based on the intracerebroventricular administration of sulfite in Wistar rats. Since treatment for MoCD is largely ineffective, we also investigated the effects of metformin, an antidiabetic drug with neuroprotective potential. Reduced basal, maximal, and ATP-linked respiration and reserve respiratory capacity were verified in MOCS1 deficient fibroblasts. The protein content of MFN1/2, OPA1, DRP1, and NRF1 was also reduced, whereas p-DRP1 (Ser 637) was increased. Su
System biology-based assessment of the molecular mechanism of epigallocatechin gallate in Parkinson's disease:… MEDIUM▼
Epigallocatechin gallate (EGCG) compound (IMPHY000226) has the potential to modulate multiple molecular mechanisms involved in Parkinson's disease. Multiple targets such as SIRT3, FOXO1, PRKAA1, PPARGC1A, and CREBBP directly regulate reactive oxygen species levels and oxidative stress, suggesting that targeting these genes could help prevent further cellular damage. EGCG targets were identified using Swiss target prediction, revealing 31 targets modulated by EGCG. Specific keywords were used to identify 4663 targets related to PD modulation. The network was constructed and analyzed using the node and edge counts. Clustering analysis identified specific target groups with high edge counts and Kappa scores, indicating potential key players in PD modulation. The targets SIRT3, FOXO1, and PPARGC1A were predicted to have the highest binding energies via dual algorithm-based molecular docking studies. The MD simulation studies were performed for the highest-docked targets, SIRT3, FOXO1, and
Lipid metabolism and immune crosstalk in fish gut-liver axis: Insights from SOCS8 knockout and dietary stress … MEDIUM▼
Metaflammation, a chronic immune response triggered by metabolic dysregulation, poses significant threats to gut-liver homeostasis in aquaculture species. To understand the progression of metaflammation, it is crucial to examine the role of SOCS8 deficiency in socs8-/- zebrafish, as this species may serve as a disease model for metabolic disorders due to the gradual dysregulation of immunity, metabolism, and the gut microbiota observed in them. This study examines the immune-metabolic crosstalk in grass carp, subjected to soybean meal-induced enteritis, and in socs8-/- zebrafish under genetic and dietary stress. SOCS8 is a negative regulator of cytokine signaling via the JAK/STAT pathway; its deficiency mirrors the persistent inflammatory and insulin-resistant states commonly seen in carnivorous fish-fed high-soybean diets, making it a valuable model for studying diet-induced metaflammation. Weighted gene co-expression network analysis (WGCNA), differential expression profiling, and im
Peroxisome proliferator-activated receptor gamma (PPAR-γ) is one of the ligand-activated transcription factors which regulates a number of central events and considered as a promising target for various neurodegenerative disease conditions. Numerous reports implicate that PPAR-γ agonists have shown neuroprotective effects by regulating genes transcription associated with the pathogenesis of neurodegeneration. In regards, this review critically appraises the recent knowledge of PPAR-γ receptors in neuroprotection in order to hypothesize potential neuroprotective mechanism of PPAR-γ agonism in chronic neurological conditions. Of note, the PPAR-γ's interaction dynamics with PPAR-γ coactivator-1α (PGC-1α) has gained significant attention for neuroprotection. Likewise, a plethora of studies suggest that the PPAR-γ pathway can be actuated by the endogenous ligands present in the CNS and thus identification and development of novel agonist for the PPAR-γ receptor holds a vow to prevent neurod
Neurons rely heavily on mitochondria for their function and survival. Mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases such as Parkinson's disease. PGC-1α is a master regulator of mitochondrial biogenesis and function. Here we identify necdin as a potent PGC-1α stabilizer that promotes mitochondrial biogenesis via PGC-1α in mammalian neurons. Expression of genes encoding mitochondria-specific proteins decreases significantly in necdin-null cortical neurons, where mitochondrial function and expression of the PGC-1α protein are reduced. Necdin strongly stabilizes PGC-1α by inhibiting its ubiquitin-dependent degradation. Forced expression of necdin enhances mitochondrial function in primary cortical neurons and human SH-SY5Y neuroblastoma cells to prevent mitochondrial respiratory chain inhibitor-induced degeneration. Moreover, overexpression of necdin in the substantia nigra in vivo of adult mice protects dopaminergic neurons against degeneration in
The constant high energy demand of neurons makes them rely heavily on their mitochondria. Dysfunction of mitochondrial energy metabolism leads to reduced ATP production, impaired calcium buffering, and generation of reactive oxygen species. There is strong evidence that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Huntington's disease (HD). Studies over the past few years have implicated an impaired function of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), a transcriptional master coregulator of mitochondrial biogenesis, metabolism, and antioxidant defenses, in causing mitochondrial dysfunction in HD. Here we have attempted to discuss in a nutshell, the key findings on the role of PGC-1α in mitochondrial dysfunction in HD and its potential as a therapeutic target to cure HD.
The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a well-known transcriptional coactivator involved in mitochondrial biogenesis. PGC-1α is implicated in the pathophysiology of many neurodegenerative disorders; therefore, a deep understanding of its functioning in the nervous system may lead to the development of new therapeutic strategies. The central nervous system (CNS)-specific isoforms of PGC-1α have been recently identified, and many functions of PGC-1α are assigned to the particular cell types of the central nervous system. In the mice CNS, deficiency of PGC-1α disturbed viability and functioning of interneurons and dopaminergic neurons, followed by alterations in inhibitory signaling and behavioral dysfunction. Furthermore, in the ALS rodent model, PGC-1α protects upper motoneurons from neurodegeneration. PGC-1α is engaged in the generation of neuromuscular junctions by lower motoneurons, protection of photoreceptors, and reduction in oxidative stress i
Retinal degenerative diseases are generally characterized by a permanent loss of light-sensitive retinal neurons known as photoreceptors, or their support cells, the retinal pigmented epithelium (RPE). Metabolic dysfunction has been implicated as a common mechanism of degeneration. In this study, we used the drug metformin in a gain-of-function approach to activate adenosine monophosphate-activated protein kinase (AMPK). We found that treatment protected photoreceptors and the RPE from acute injury and delayed inherited retinal degeneration. Protection was associated with decreased oxidative stress, decreased DNA damage, and increased mitochondrial energy production. To determine whether protection was a local or a systemic effect of metformin, we used AMPK retinal knockout mice and found that local expression of AMPK catalytic subunit α2 was required for metformin-induced protection. Our data demonstrate that increasing the activity of AMPK in retinal neurons or glia can delay or prev
Reactive microglia are a major pathological feature of Alzheimer's disease (AD). However, the exact role of microglia in AD pathogenesis is still unclear. Here, using metabolic profiling, we found that exposure to amyloid-β triggers acute microglial inflammation accompanied by metabolic reprogramming from oxidative phosphorylation to glycolysis. It was dependent on the mTOR-HIF-1α pathway. However, once activated, microglia reached a chronic tolerant phase as a result of broad defects in energy metabolisms and subsequently diminished immune responses, including cytokine secretion and phagocytosis. Using genome-wide RNA sequencing and multiphoton microscopy techniques, we further identified metabolically defective microglia in 5XFAD mice, an AD mouse model. Finally, we showed that metabolic boosting with recombinant interferon-γ treatment reversed the defective glycolytic metabolism and inflammatory functions of microglia, thereby mitigating the AD pathology of 5XFAD mice. Collectively,
Cordycepin Modulates Microglial M2 Polarization Coupled with Mitochondrial Metabolic Reprogramming by Targetin… STRONG▼
The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG-M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG-M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC-MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investi
Metabolic reprogramming in inflammatory microglia indicates a potential way of targeting inflammation in Alzhe… STRONG▼
Microglia activation drives the pro-inflammatory activity in the early stages of Alzheimer's disease (AD). However, the mechanistic basis is elusive, and the hypothesis of targeting microglia to prevent AD onset is little explored. Here, we demonstrated that upon LPS exposure, microglia shift towards an energetic phenotype characterised by high glycolysis and high mitochondrial respiration with dysfunction. Although the activity of electron transport chain (ETC) complexes is boosted by LPS, this is mostly devoted to the generation of reactive oxygen species. We showed that by inhibiting succinate dehydrogenase (SDH) with dimethyl malonate (DMM), it is possible to modulate the LPS-induced metabolic rewiring, facilitating an anti-inflammatory phenotype. DMM improves mitochondrial function in a direct way and by reducing LPS-induced mitochondrial biogenesis. Moreover, the block of SDH with DMM inhibits the recruitment of hypoxia inducible-factor 1 α (HIF-1α), which mediates the induction
As intrinsic immune cells in the central nervous system, microglia play a crucial role in maintaining brain homeostasis. Microglia can transition from homeostasis to various responsive states in reaction to different external stimuli, undergoing corresponding alterations in glucose metabolism. In neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), microglial glucose metabolic reprogramming is widespread. This reprogramming leads to changes in microglial function, exacerbating neuroinflammation and the accumulation of pathological products, thereby driving the progression of neurodegeneration. This review summarizes the specific alterations in glucose metabolism within microglia in AD, PD, ALS, and MS, as well as the corresponding treatments aimed at reprogramming glucose metabolism. Compounds that inhibit key glycolytic enzymes like hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2), or
✗ Opposing Evidence 9
Polystyrene microplastics induced spermatogenesis disorder via disrupting mitochondrial function through the r… MEDIUM▼
Microplastics (MPs) have emerged as hazardous substances, eliciting widespread concern regarding their potential toxicity. Although our previous research has indicated that polystyrene MPs (PS-MPs) might cause male reproductive toxicity in mammals, their precise effects on sperm motility parameters and acrosomal development remain uncertain. Herein, the effects on sperm motility of PS-MPs at varied particle sizes (0.5 μm, 4 μm and 10 μm) and the underlying mechanisms were examined. The results revealed that PS-MPs caused a decrease in sperm motility, accompanied by abnormalities in the structure and function of the sperm acrosome. Meanwhile, PS-MPs triggered the elevation of intracellular reactive oxygen species levels and the abnormal expression of antioxidant enzymes (γH2AX, GPX4, Peroxiredoxin 5 and SDHB), indicating disruption of the sperm antioxidant system. Furthermore, we observed aberrant expression of key factors involved in mitochondrial fission/fusion (Drp1, Fis1, Mfn1, Mfn2
Ropivacaine is one of the commonly used local anesthetics in medical and dental care. However, preclinical and observational studies indicate that ropivacaine could have substantial side effects including neurotoxicity, which has raised concern regarding the safety of this drug. In the present study, we investigated the effects of clinically relevant doses of ropivacaine on mitochondrial biogenesis and function in neuronal cells. Our data indicate that exposure to ropivacaine leads to reduced expression of the major mitochondrial regulator PGC-1α and its downstream transcription factors NRF1 and TFAM. Ropivacaine treatment induces impairment of mitochondrial biogenesis by reducing mitochondrial mass, the ratio of mtDNA to nDNA (mtDNA/nDNA), cytochrome C oxidase activity, and COX-1 expression. Additionally, treatment with ropivacaine causes "loss of mitochondrial function" by impairing the mitochondrial respiratory rate and ATP production. Mechanistically, the reduction of PGC-1α caused
Di-2-ethylhexyl phthalate (DEHP) and Dioctyl phthalate (DnOP) are widely used as plasticizers in various industries for which the consequent health problems are of great concern. In this context, we treated HepG2 cells with DEHP or DnOP for 48 h. The results showed that DEHP and DnOP caused increase in oxygen species (ROS), malondialdehyde (MDA), Alanine aminotransferase (ALT) and Aspartate transaminase (AST). The proteins NF⁃E2-related factor 2 (Nrf2) and haemeoxygenase-1 (HO-1), were significantly down-regulated. Subsequently, the mitochondrial structure was disrupted, and the ATP content, the mitochondrial copy number as well as the expression of the corresponding mitochondrial genes were also reduced. The expression of sirtuin 1(SIRT1), PPAR gamma co-activator 1 alpha (PGC-1α), Nuclear respiratory factor 1(Nrf1), Mitochondrial transcription factor A (TFAM) on the SIRT1/PGC-1α pathway were significantly reduced. Finally, neither DEHP nor DnOP was found to induce apoptosis, but could
Pgc-1α overexpression downregulates Pitx3 and increases susceptibility to MPTP toxicity associated with decrea… MEDIUM▼
Multiple mechanisms likely contribute to neuronal death in Parkinson's disease (PD), including mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1α) positively regulates the expression of genes required for mitochondrial biogenesis and the cell's antioxidant responses. Also, expression of PGC-1α-regulated genes is low in substantia nigra (SN) neurons in early PD. Thus upregulation of PGC-1α is a candidate neuroprotective strategy in PD. Here, an adeno-associated virus (AAV) was used to induce unilateral overexpression of Pgc-1α, or a control gene, in the SN of wild-type C57BL/6CR mice. Three weeks after AAV administration, mice were treated with saline or MPTP. Overexpression of Pgc-1α in the SN induced expression of target genes, but unexpectedly it also greatly reduced the expression of tyrosine hydroxylase (Th) and other markers of the dopaminergic phenotype with resultant severe loss of striatal dopamine. Redu
p75NTR Modulation by LM11A-31 Counteracts Oxidative Stress and Cholesterol Dysmetabolism in a Rotenone-Induced… MEDIUM▼
The p75 neurotrophin receptor (p75NTR) plays a dual role in regulating both pro-survival and pro-apoptotic cascades in various physiological and pathological conditions, including within dopaminergic neuronal population. Notably, its overexpression has been documented in post-mortem Parkinson's disease (PD) brains, where it correlates with a significant downregulation in neuroprotective intracellular mediators. In this study, we aimed at investigating the neuroprotective effects of p75NTR modulation by the small molecule LM11A-31 in a rotenone-induced neuronal model of PD. Differentiated SH-SY5Y cells were treated with 100 nM rotenone, with or without 500 nM LM11A-31. Our results show that LM11A-31 effectively mitigates PD phenotype by enhancing cell viability, reducing apoptosis, mitigating α-synuclein aggregation, and partially restoring neuromorphological features. Mitochondrial integrity was preserved, likely through the upregulation of transcription factors involved in mitochondri
PSMD4 Alleviates Aβ₁₋₄₂-Induced Mitochondrial Dysfunction and Oxidative Stress via the PGC-1α/Nrf Axis in Alzh… MEDIUM▼
This study aimed to investigate the role of 26S proteasome non-ATPase regulatory subunit 4 (PSMD4) in regulating mitochondrial function and oxidative stress in Alzheimer's disease (AD) and to explore its potential molecular mechanism in Aβ-induced neurotoxicity. An in vitro AD model was established by treating Neuro-2a cells with Aβ₁₋₄₂, and PSMD4 was overexpressed using a lentiviral vector. Flow cytometry was employed to assess reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm). Quantitative PCR and Western blotting were utilized to examine the expression of mitochondrial biogenesis-associated regulators, including PGC-1α, Nrf1, Nrf2, and TFAM. For the in vivo study, APP/PS1 double-transgenic mice served as the AD model. Histological analyses (HE and Nissl staining), immunofluorescence, and Western blotting were performed to evaluate hippocampal neuronal morphology and the expression of PSMD4 and mitochondrial marker TOM20. Aβ₁₋₄₂ significantly increas
Atherosclerosis imposes a heavy burden on cardiovascular health due to its indispensable role in the pathogenesis of cardiovascular disease (CVD) such as coronary artery disease and heart failure. Ample clinical and experimental evidence has corroborated the vital role of inflammation in the pathophysiology of atherosclerosis. Hence, the demand for preclinical research into atherosclerotic inflammation is on the horizon. Indeed, the acquisition of an in-depth knowledge of the molecular and cellular mechanisms of inflammation in atherosclerosis should allow us to identify novel therapeutic targets with translational merits. In this review, we aimed to critically discuss and speculate on the recently identified molecular and cellular mechanisms of inflammation in atherosclerosis. Moreover, we delineated various signaling cascades and proinflammatory responses in macrophages and other leukocytes that promote plaque inflammation and atherosclerosis. In the end, we highlighted potential the
Alzheimer's disease is a chronic illness with long preclinical and prodromal phases (20 years) and an average clinical duration of 8-10 years. The disease has an estimated prevalence of 10-30% in the population >65 years of age with an incidence of 1-3%. Most patients with Alzheimer's disease (>95%) have the sporadic form, which is characterized by a late onset (80-90 years of age), and is the consequence of the failure to clear the amyloid-β (Aβ) peptide from the interstices of the brain. A large number of genetic risk factors for sporadic disease have been identified. A small proportion of patients (<1%) have inherited mutations in genes that affect processing of Aβ and develop the disease at a much younger age (mean age of ∼45 years). Detection of the accumulation of Aβ is now possible in preclinical and prodromal phases using cerebrospinal fluid biomarkers and PET. Several approved drugs ameliorate some of the symptoms of Alzheimer's disease, but no current interventions can modify
Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzh… MEDIUM▼
INTRODUCTION: Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD and its sequential association with core AD biomarkers is poorly understood. METHODS: Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS) in participants with AD dementia (n = 47), mild cognitive impairment (MCI; n = 137), and normal controls (n = 235) from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: ALPS index was significantly lower in AD dementia than in MCI or controls. Lower ALPS index was significantly associated with faster changes in amyloid positron emission tomography (PET) burden and AD signature region of interest volume, higher risk of amyloid-positive transition and clinical progression, and faster rates of amyloid- and neurodegeneration-related cognitive decline. Furthermore, the associations of the ALPS index with cognitive decline
🧬 Theorist Proposes novel mechanisms and generates creative hypotheses ▼
Novel Therapeutic Hypotheses for Pre-Clinical Neurodegeneration
Hypothesis 1: Circadian-Synchronized Proteostasis Enhancement
Title: Chronotherapy-Based Protein Clearance AmplificationDescription: Digital biomarkers revealing disrupted sleep-wake cycles and motor fluctuations indicate circadian dysregulation occurring years before clinical diagnosis. Precisely timed administration of autophagy enhancers and proteasome activators during optimal circadian windows could amplify endogenous protein clearance mechanisms. This approach leverages the natural circadian regulation of gly
🔍 Skeptic Identifies weaknesses, alternative explanations, and methodological concerns ▼
Critical Evaluation of Novel Therapeutic Hypotheses
Hypothesis 1: Circadian-Synchronized Proteostasis Enhancement
Specific Weaknesses
- Therapeutic window uncertainty: No evidence provided for optimal timing windows, which likely vary significantly between individuals and disease states
- Drug delivery challenges: Assumes proteostasis enhancers can achieve therapeutic CNS concentrations at specific times without addressing pharmacokinetic constraints
- Circadian disruption causality: Evidence shows correlation between circadian disruption and neurodegeneration, but causa
🎯 Domain Expert Assesses practical feasibility, druggability, and clinical translation ▼
Druggability and Feasibility Assessment
Hypothesis 1: Circadian-Synchronized Proteostasis Enhancement
Revised Confidence: 0.45Druggability Assessment
CLOCK/BMAL1 Targets:- Low druggability: Transcription factors are notoriously difficult to target directly
- Alternative approach: Target upstream kinases (CK1δ/ε, GSK-3β) or nuclear hormone receptors (REV-ERBα/β)
- High druggability: Kinase with defined ATP-binding pocket
- Existing chemical matter: Multiple tool compounds available
Existing Compounds/Clinical Candidates
**Autophag
⚖ Synthesizer Integrates perspectives and produces final ranked assessments ▼
Price History
| Event | Price | Change | Source | Time | |
|---|---|---|---|---|---|
| ⚖ | Recalibrated | $0.604 | market_dynamics | 2026-04-13 03:33 | |
| ⚖ | Recalibrated | $0.604 | ▼ 0.4% | 2026-04-12 18:34 | |
| ⚖ | Recalibrated | $0.606 | ▼ 0.2% | 2026-04-12 10:15 | |
| ⚖ | Recalibrated | $0.608 | ▼ 0.7% | 2026-04-12 05:13 | |
| ⚖ | Recalibrated | $0.612 | ▼ 0.5% | 2026-04-10 15:58 | |
| ⚖ | Recalibrated | $0.615 | ▲ 0.5% | 2026-04-10 15:53 | |
| ⚖ | Recalibrated | $0.611 | ▲ 3.6% | 2026-04-08 18:39 | |
| ⚖ | Recalibrated | $0.590 | ▲ 5.5% | 2026-04-06 04:04 | |
| ⚖ | Recalibrated | $0.559 | ▼ 0.9% | 2026-04-04 16:38 | |
| ⚖ | Recalibrated | $0.564 | ▲ 1.9% | 2026-04-04 16:02 | |
| ⚖ | Recalibrated | $0.554 | ▼ 0.6% | 2026-04-04 01:39 | |
| ⚖ | Recalibrated | $0.557 | ▼ 4.9% | 2026-04-03 23:46 | |
| ⚖ | Recalibrated | $0.586 | ▼ 3.5% | 2026-04-02 21:55 | |
| ⚖ | Recalibrated | $0.607 | ▼ 0.9% | market_recalibrate | 2026-04-02 19:14 |
| 📊 | Score Update | $0.612 | ▲ 2.2% | market_dynamics | 2026-04-02 13:37 |
Clinical Trials (6) Relevance: 45%
Active
Completed
Total Enrolled
Highest Phase
📚 Cited Papers (44)
📓 Linked Notebooks (1)
Wiki Pages
KG Entities (62)
Dependency Graph (2 upstream, 3 downstream)
Linked Experiments (10)
Related Hypotheses
Estimated Development
🧪 Falsifiable Predictions (2)
Knowledge Subgraph (313 edges)
activates (1)
associated with (20)
co associated with (21)
encodes (1)
implicated in (7)
initiates (1)
maintains (1)
master regulator (1)
modulates (1)
participates in (13)
preserves (1)
prevents (1)
promoted: Circadian-Synchronized Proteostasis Enhancement (1)
promoted: Digital Twin-Guided Metabolic Reprogramming (1)
promoted: Multi-Modal Stress Response Harmonization (1)
promoted: Smartphone-Detected Motor Variability Correction (1)
transcriptional complex (1)
Mechanism Pathway for PPARGC1A/PRKAA1
Molecular pathway showing key causal relationships underlying this hypothesis
graph TD
PPARGC1A_PRKAA1["PPARGC1A/PRKAA1"] -->|promoted: Digital | neurodegeneration["neurodegeneration"]
PPARGC1A_PRKAA1_1["PPARGC1A/PRKAA1"] -->|associated with| neurodegeneration_2["neurodegeneration"]
CLOCK_ULK1["CLOCK/ULK1"] -->|co associated with| PPARGC1A_PRKAA1_3["PPARGC1A/PRKAA1"]
DRD2_SNCA["DRD2/SNCA"] -->|co associated with| PPARGC1A_PRKAA1_4["PPARGC1A/PRKAA1"]
FOXP3_TGFB1["FOXP3/TGFB1"] -->|co associated with| PPARGC1A_PRKAA1_5["PPARGC1A/PRKAA1"]
NR3C1_CRH_TNFA["NR3C1/CRH/TNFA"] -->|co associated with| PPARGC1A_PRKAA1_6["PPARGC1A/PRKAA1"]
PDGFRB_ANGPT1["PDGFRB/ANGPT1"] -->|co associated with| PPARGC1A_PRKAA1_7["PPARGC1A/PRKAA1"]
CHR2_BDNF["CHR2/BDNF"] -->|co associated with| PPARGC1A_PRKAA1_8["PPARGC1A/PRKAA1"]
style PPARGC1A_PRKAA1 fill:#ce93d8,stroke:#333,color:#000
style neurodegeneration fill:#ef5350,stroke:#333,color:#000
style PPARGC1A_PRKAA1_1 fill:#ce93d8,stroke:#333,color:#000
style neurodegeneration_2 fill:#ef5350,stroke:#333,color:#000
style CLOCK_ULK1 fill:#ce93d8,stroke:#333,color:#000
style PPARGC1A_PRKAA1_3 fill:#ce93d8,stroke:#333,color:#000
style DRD2_SNCA fill:#ce93d8,stroke:#333,color:#000
style PPARGC1A_PRKAA1_4 fill:#ce93d8,stroke:#333,color:#000
style FOXP3_TGFB1 fill:#ce93d8,stroke:#333,color:#000
style PPARGC1A_PRKAA1_5 fill:#ce93d8,stroke:#333,color:#000
style NR3C1_CRH_TNFA fill:#ce93d8,stroke:#333,color:#000
style PPARGC1A_PRKAA1_6 fill:#ce93d8,stroke:#333,color:#000
style PDGFRB_ANGPT1 fill:#ce93d8,stroke:#333,color:#000
style PPARGC1A_PRKAA1_7 fill:#ce93d8,stroke:#333,color:#000
style CHR2_BDNF fill:#ce93d8,stroke:#333,color:#000
style PPARGC1A_PRKAA1_8 fill:#ce93d8,stroke:#333,color:#000
Predicted Protein Structure
🔮 PPARGC1A — AlphaFold Prediction Q9UBK2 Click to expand 3D viewer
Source Analysis
Digital biomarkers and AI-driven early detection of neurodegeneration
neurodegeneration | 2026-04-01 | completed