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Hypotheses

1,878 items
IdTitleComposite ScoreConfidence ScoreTarget GeneStatusCreated AtAnalysis Id
h-alsmnd-e448328ae29GLE1-Mediated mRNA Export Defect Creates Translation-Competent mRNA Starvation i0.830.75GLE1,DBP10,EXPORTIN-1,XPO1,mRNA export machinery,NPCopen2026-04-28
h-var-a0933e666dMicroglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuro0.820.76AIM2, CASP1, IL1B, PYCARD, TARDBPproposed2026-04-05SDA-2026-04-01-gap-20260401-225149
h-22d2cfcdSIRT1 Activation Couples Mitochondrial Biogenesis to Ferroptosis Suppression via0.820.50SIRT1 and PGC1alpha (PPARGC1A) axisproposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-174000-6451afef
h-43f72e21AMPK hypersensitivity in astrocytes creates enhanced mitochondrial rescue respon0.820.65PRKAA1promoted2026-04-02sda-2026-04-01-gap-v2-89432b95
h-var-adfecef68aAstrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates 0.820.78NLRP3, CASP1, IL1B, PYCARDproposed2026-04-05SDA-2026-04-01-gap-20260401-225149
h-856feb98Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation0.820.78BDNFpromoted2026-04-02SDA-2026-04-03-26abc5e5f9f2
h-ff0d545dHSPB1 Phosphorylation Mimetics to Promote Protective TDP-43 Liquid-Liquid Phase 0.820.68HSPB1promoted2026-04-13SDA-2026-04-12-gap-debate-20260410-113051-5dce7651
h-0ca0f0f8f2TREM2 Deficiency Drives Microglial Senescence via Lipid Metabolism Dysregulation0.820.82TREM2/TYROBPdebated2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041439-5f43216e
h-alsmnd-01446b71d93MATR3 Nuclear Body Disruption Impairs RNA Processing Hubs and Triggers Splicing 0.820.75MATR3,U1 snRNP,SNRPB,SNRNP70, splicing machinery,spliceosomeopen2026-04-28
SDA-2026-04-02-gap-tExtracellular Vesicle Biogenesis Modulation0.810.57CHMP4Bproposed2026-04-17SDA-2026-04-04-gap-tau-prop-20260402003221
h-5d100034SLC7A11 System Activation Restores Cystine Uptake and GSH Synthesis to Prevent N0.810.47SLC7A11 (system Xc-) and GPX4proposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-174000-6451afef
h-0bcda2e0CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerabilit0.810.78APOE, CLUpromoted2026-04-16SDA-2026-04-15-gap-debate-20260410-112607-0a3749ea
h-alsmnd-54f981ca6a2TIA1 Low-Complexity Domain Oxidation Drives Aberrant Stress Granule Assembly and0.810.75TIA1,TDP-43,TARDBP,G3BP1,MAPK1,Oxidative stress responseopen2026-04-28
SDA-2026-04-02-gap-tLRP1-Dependent Tau Uptake Disruption0.810.72LRP1promoted2026-04-17SDA-2026-04-04-gap-tau-prop-20260402003221
h-0cbe9bacCSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion0.810.52CSF1R-TREM2proposed2026-04-17SDA-2026-04-01-gap-001
h-5b35f7a5Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to Neuro0.810.62HCAR2promoted2026-04-16SDA-2026-04-15-gap-debate-20260410-112330-9abf86eb
h-3b539acfNeutrophil Extracellular Trap (NET) Inhibition0.810.86PADI4proposed2026-04-16SDA-2026-04-16-gap-bbb-tjp-20260416041707
h-var-6957745feaMitochondrial DAMPs-Driven AIM2 Inflammasome Activation in Neurodegeneration0.810.75AIM2, CASP1, IL1B, PYCARDproposed2026-04-05SDA-2026-04-01-gap-20260401-225149
h-var-af9eb8e59bCalcium-Dysregulated mPTP Opening as an Alternative mtDNA Release Mechanism for 0.800.75AIM2, CASP1, IL1B, PYCARD, PPIFproposed2026-04-05SDA-2026-04-01-gap-20260401-225149
h-2e03f316TREM2-mTOR Co-Agonism for Metabolic Reprogramming0.800.60TREM2-mTOR pathwayproposed2026-04-17SDA-2026-04-01-gap-001
h-48d1115aDual-Receptor Antibody Shuttling0.800.45proposed2026-04-13
h-d47c2efaTargeting the Mechanistic Link Between AQP4 Dysfunction and Ferroptosis Prevents0.800.52AQP4 and ACSL4 (key ferroptosis regulator)proposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-174000-6451afef
h-var-d04a952932Mitochondrial DNA-Driven AIM2 Inflammasome Activation in Neurodegeneration0.800.74AIM2, CASP1, IL1B, PYCARDsuperseded2026-04-05SDA-2026-04-01-gap-20260401-225149
h-7d24e096CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Window Identification0.800.80sTREM2/membrane-TREM2/ADAM10promoted2026-04-16SDA-2026-04-26-trem2-showcase
h-var-22c38d11cdACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degen0.800.87ACSL4debated2026-04-05SDA-2026-04-03-gap-seaad-v4-20260402065846
h-var-261452bfb440 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively 0.800.87ACSL4debated2026-04-05SDA-2026-04-03-gap-seaad-v4-20260402065846
h-7e9718dbdapH-Sensitive Bispecific Antibody Targeting Transferrin Receptor for CNS Delivery0.800.33TFRC (TfR1); endosomal acidification pathwayproposed2026-04-22SDA-2026-04-02-gap-bbb-antibody-transport
h-f32ba823Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective Effector0.800.52MANF, CDNFproposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-170057-a2f72fd8
h-48858e2aMicroglial TREM2-SYK Pathway Enhancement0.800.70TREM2promoted2026-04-14SDA-2026-04-03-gap-seaad-v4-20260402065846
h-var-ee70969116Closed-loop transcranial focused ultrasound targeting CA1 PV interneurons with r0.800.45PVALBproposed2026-04-07SDA-2026-04-03-26abc5e5f9f2
h-11795af0Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)0.790.30APOEpromoted2026-04-02sda-2026-04-01-gap-010
h-a9f2570bTargeting SASP-Complement Amplification Through HIF-1α Downstream Effectors0.790.68C1QA, C1QB, C3, IL1Bpromoted2026-04-14SDA-2026-04-13-gap-pubmed-20260410-170057-1bea7d88
h-3f02f222Senescent Microglia Resolution via Maresins-Senolytics Combination0.790.60BCL2L1debated2026-04-02sda-2026-04-01-gap-014
h-ac41e5c23dExposed amyloidogenic segments (β-sheet propensity residues) serve as HSP70 reco0.790.72HSPA8, HSPA1A, DNAJB6, DNAJB2proposed2026-04-21SDA-2026-04-10-gap-debate-20260410-075012-32bac138
h-d4ac0303f6G2019S primarily raises baseline LRRK2 kinase activity rather than amplifying ly0.790.32LRRK2proposed2026-04-25SDA-2026-04-25-gapdebate-9180363b7c
h-da9af6a77aNMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic Axis and Dopaminergic0.790.73SIRT1/NAD+ axisproposed2026-04-22SDA-2026-04-04-gap-20260404-060512
h-f3fb3b91Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflammatory Priming0.790.60TLR4proposed2026-04-03SDA-2026-04-01-gap-20260401-225149
SDA-2026-04-02-gap-tVCP-Mediated Autophagy Enhancement0.790.53VCPproposed2026-04-17SDA-2026-04-04-gap-tau-prop-20260402003221
hyp-SDA-2026-04-12-2Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbates Amyloid Pathology0.790.55CHRNA7 (α7 nicotinic receptor), BACE1debated2026-04-13SDA-2026-04-12-20260411-082446-2c1c9e2d
h-d0a564e8Competitive APOE4 Domain Stabilization Peptides0.780.30APOEpromoted2026-04-02sda-2026-04-01-gap-010
h-ecd9ed6cIntegrated Biomarker Panel for Therapeutic Window Identification0.780.68CHI3L1promoted2026-04-16SDA-2026-04-15-gap-debate-20260410-112330-9abf86eb
h-var-d98a992599Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activa0.780.72SSTproposed2026-04-05SDA-2026-04-03-26abc5e5f9f2
hyp-lyso-snca-1d58cfLAMP2A Liquid-Liquid Phase Separation Defects in Dopaminergic Neurons Create Sel0.780.68LAMP2active2026-04-28
h-01685bc3b9Differential Complement Regulator Expression on Synaptic Membranes (CD55/CD46)0.780.72CD55 (DAF), CD46 (MCP)proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062128-c84a87d9
h-807d7a82SASP-Driven Aquaporin-4 Dysregulation0.780.70AQP4promoted2026-04-02sda-2026-04-01-gap-013
SDA-2026-04-02-gap-tTREM2-mediated microglial tau clearance enhancement0.780.67TREM2proposed2026-04-17SDA-2026-04-04-gap-tau-prop-20260402003221
h-9923279defPINK1/Parkin–TREM2 Axis: Convergent Mitophagy Failure Unifies PD (SNCA/αSyn) and0.780.72PINK1,PRKN,TREM2,STUB1,NDUFS7proposed2026-04-28
h-7000ac15c1Therapeutic Window Exists Because Amplified Signals (Not Baseline) Drive Pathoge0.780.78LRRK2proposed2026-04-26SDA-2026-04-23-gap-debate-20260417-033119-54941818
h-dec9f2e970NLRP3 Inhibition (H7): Downstream Inflammatory Reversal0.780.78NLRP3/NLRP3 (NLRP3 inflammasome)proposed2026-04-26SDA-2026-04-26-gap-pubmed-20260410-180918-962b1ada-debate
h-17d177c62bSleep-Dependent Glymphatic Clearance Expands the Therapeutic Window by Reducing 0.780.78AQP4, orexin receptor (HCRTR1/2)proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062052-7bcf4b6c
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