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Hypotheses

2,369 items
IdTitleComposite ScoreConfidence ScoreTarget GeneStatusCreated AtAnalysis Id
h-9a108e26Pharmacological Enhancement of APOE4 Glycosylation0.620.58ST6GAL1, FUT8debated2026-04-02sda-2026-04-01-gap-010
h-1e28311bMicroglial ACE Enhancement for Amyloid Clearance0.620.40ACEproposed2026-04-04SDA-2026-04-03-gap-aging-mouse-brain-v3-20260402
h-40fbbb01SYNJ1 Aggregation and Solubility Loss Impairs PI(4,5)P2 Cycling at Synaptic Term0.620.62SYNJ1, INPP5A, PIK3CA, PLCG1proposed2026-04-17SDA-2026-04-16-gap-debate-20260411-065018-92a34465
h-ee1df336Vagal Afferent Microbial Signal Modulation0.620.70GLP1R, BDNFproposed2026-04-02SDA-2026-04-01-gap-20260401-225155
h-346639e8Designer TRAK1-KIF5 fusion proteins accelerate therapeutic mitochondrial deliver0.620.30TRAK1_KIF5Adebated2026-04-02sda-2026-04-01-gap-v2-89432b95
h-6657f7cdSphingolipid Metabolism Reprogramming0.620.30CERS2debated2026-04-02sda-2026-04-01-gap-005
h-28c25ed899OPC Maturation Block via PDGFRA/LXRβ0.620.60PDGFRAproposed2026-04-28SDA-2026-04-28-gap-methodol-20260427-041425-9e73b245
h-f0e5efbf54CDK5 Inhibition Blocks Activity-Dependent Tau Propagation0.620.68CDK5proposed2026-04-28SDA-TEST-PREREG-003
h-7094b1202cLRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysosomal Enhancement0.620.75LRRK2proposed2026-04-26test-hypothesis-fixtures-v1
h-8af96e9ea0NLRP3 Inflammasome Priming Converts SCFA-Sensitive Pyroptosis into Chronic IL-1β0.620.70NLRP3, CASP1, GSDMD, IL1B, IL1R1, C3, C1QA, GPR109A (HCAR2)proposed2026-04-26SDA-2026-04-26-gap-20260425-225305
h-gwas-trem2-abi3-phTREM2-ABI3 actin-phagocytosis coupling is a higher-yield AD target than either l0.620.62TREM2/ABI3proposed2026-04-26
h-3a8f13acSenescence-Associated Epigenetic Phenotype (SEP)0.620.65Senescence-Associated Epigenetic Phenotypeproposed2026-04-26SDA-2026-04-19-gap-epigenetic-comparative-ad-pd-als
h-c5dd93610aLocus coeruleus degeneration gates whether cholinergic dysfunction or amyloid/ta0.620.58DBH, ADRB1, ADRB2proposed2026-04-25SDA-2026-04-25-gapdebate-e849205bca
h-aefb475d5cTau fibrils expose neuronal phosphatidylserine and heat-shock protein 70, drivin0.620.65Phosphatidylserine, TIMD4, HSPA1A/HSPA1B, SCARF1, LRP8proposed2026-04-22SDA-2026-04-02-gap-synaptic-pruning-microglia
h-e8432692ffNuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulation in ALS-FTD0.620.20TARDBP, splicing targets (Sortilin1, Synaptojanin1)proposed2026-04-22SDA-2026-04-02-gap-2026-04-01-gap-006
h-5faf622cdcSubtle NMDAR Inhibition Attenuates Excitotoxicity-Driven Tau Release from Hypers0.620.65GRIN2Bproposed2026-04-22SDA-2026-04-04-gap-20260404-052358
h-b4e8a2f6f9Selective cathepsin B inhibition prevents cathepsin leakage-mediated NLRP3 infla0.620.65CTSBproposed2026-04-22SDA-2026-04-04-gap-lysosomal-cathepsin-ad
h-a93292f54fMetabolic Rewiring via SPP1-Induced HIF1α Glycolytic Shift0.620.62HIF1A (HIF1α), MTOR (mTORC1), EGLN1 (PHD2)proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-062118-e3613755
h-0addc33bbeEnhanced MCU Activity Primes mPTP Opening in Motor Neurons0.620.60MCU complex (MICU1/MICU2), mitochondrial calcium regulatory proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062141-611cf046
h-9318aa358dC1Q-Induced Foam Cell Formation via Scavenger Receptor Upregulation0.620.58C1QA/C1QCproposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062122-b65f8ebc
h-65a83ac920CX3CR1-Targeted HDAC3 Knockdown in Microglia via AAV9 Delivery0.620.72HDAC3 (class I histone deacetylase)proposed2026-04-21SDA-2026-04-08-gap-debate-20260406-062039-47e9c8cf
h-a00d94b8c8Synaptic RNA Metabolism Dysregulation0.620.75TARDBPproposed2026-04-21SDA-2026-04-08-gap-pubmed-20260406-062202-5c32c50a
h-b7248a5c60TET Enzyme-Mediated 5hmC Restoration as Neuronal Rejuvenation Strategy0.620.65TET2; TET3proposed2026-04-21SDA-2026-04-10-gap-20260410-091440
h-ce92f26308SUV39H1 Restoration Represses Aberrant Transposon Expression in Aging Neurons0.620.62SUV39H1 (KMT1A)proposed2026-04-21SDA-2026-04-10-gap-20260410-091440
h-aecdf76bMicroglial xCT/SLC7A11 Selective Inhibition to Reduce Non-Cell-Autonomous Glutam0.620.62SLC7A11proposed2026-04-17SDA-2026-04-16-gap-ferroptosis-als-d2fb6bf796ed
h-a5186bb8H7: Enteric Nervous System Alpha-Synuclein Propagation Blocker via Gut Barrier R0.620.72IL-22, REG3G, zonulinpromoted2026-04-16SDA-2026-04-15-gap-pubmed-20260411-093924-7330920b
h-a62fe64aTREM2 Agonism to Reprogram Infiltrated Monocytes Toward Neuroprotective Phenotyp0.620.70TREM2promoted2026-04-13SDA-2026-04-13-gap-debate-20260411-064946-4940f331
h-019c56c1Cross-Cell Type Synaptic Rescue via Tripartite Synapse Restoration0.620.65SYN1, SLC1A2, and CX3CR1proposed2026-04-04SDA-2026-04-03-gap-seaad-v2-20260402032945
h-bc635955CSF Biomarker-Guided ABCA7 Therapeutic Dosing0.620.70ABCA7 with biomarker-guided dosingpromoted2026-04-14SDA-2026-04-14-gap-pubmed-20260410-180532-e8930cb8
h-6b394be1Lysosomal pH Restoration Upstream of TFEB0.620.60ATP6V1Aproposed2026-04-04SDA-2026-04-03-gap-debate-20260403-222617-8eb5bdbc
h-f811f090acLPS-TLR4-NF-κB Signaling Cascade as Therapeutic Target0.620.58TLR4/NFKB1/NLRP3proposed2026-04-26SDA-2026-04-26-gut-brain-pd-ffdff6f4
h-61196adeTREM2-Dependent Microglial Senescence Transition0.620.55TREM2promoted2026-04-03SDA-BIOMNI-SCRNA_AN-248caecc
h-630942bd30PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Mediates Aβ-Induced SPP1 Upregulat0.620.58SPP1proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-062118-5e49e14f
h-c6c1143bcdComplement Cascade Specificity: Microglial C3aR Antagonism Downstream of SPP10.620.58C3/C3aRproposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062118-2cdbb0dd
h-a01166eeBH4 Cofactor Restoration as Primary Driver of >500-Fold Dopamine Elevation0.620.45GCH1, TH, BH4 pathwayproposed2026-04-14SDA-2026-04-13-gap-pubmed-20260410-145531-5c4e7b59
h-b234254cTREM2-mediated microglial tau clearance enhancement0.620.52TREM2archived2026-04-02SDA-2026-04-04-gap-tau-prop-20260402003221
h-69d383eaLow Complexity Domain Cross-Linking Inhibition0.620.30TGM2debated2026-04-02sda-2026-04-01-gap-006
h-e20cf87fb3LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasome Activation and SPP0.620.52SPP1proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-062118-5e49e14f
h-8f9633d9Perinatal Immune Challenge Prevention0.620.20Multipledebated2026-04-04SDA-2026-04-04-gap-20260404-microglial-priming-early-ad
h-ba11ca72NAMPT-Centered NAD+ Restoration to Reverse Basal Forebrain Cholinergic Neuron Me0.620.65NAMPT,SIRT1,PGC1Aproposed2026-04-17SDA-2026-04-16-gap-pubmed-20260411-082446-2c1c9e2d
h-80ff3fd6Spatially-Targeted Regional Vulnerability Prevention0.620.40Regional vulnerability genesproposed2026-04-14SDA-2026-04-03-gap-seaad-v4-20260402065846
h-e8d49d4cbcMFN2-PACS2 Axis at MAMs Coordinates Mitophagy-ER-Phagy Sync0.610.60MFN2 (MFN2), PACS2 (PACS2)proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062132-e71b3ef7
h-fe1dfe730eMitophagy collapse via PINK1-PRKN is the primary autophagy lesion after irradiat0.610.56PINK1proposed2026-04-26SDA-2026-04-26-gap-pubmed-20260410-193006-9525a13b-debate
h-b47073b186Glial-Autophagy-Senescence Coupling Defines CNS Therapeutic Windows0.610.55TFEB, MAPK14, MAPKAPK2, IL6, CXCL1proposed2026-04-21SDA-2026-04-07-gap-debate-20260406-062101-724971bc
h-5e85ca4fDose-Response Framework: PINK1/Parkin Mitophagy as the Critical Mediator Linking0.610.60PINK1proposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-181340-8acb24dc
h-8f285020Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuroinflammatory Cascade0.610.30AGERproposed2026-04-03SDA-2026-04-01-gap-20260401-225149
h-297a9dcbfaFUS Mutations Alter Stress Granule Material Properties to Confer Autophagy Resis0.610.62FUSproposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041423-3a6aa4ab
h-3a4f2027Trinucleotide Repeat Sequestration via CRISPR-Guided RNA Targeting0.610.50HTT, DMPK, repeat-containing transcriptsproposed2026-04-03SDA-2026-04-03-gap-crispr-neurodegeneration-20260402
h-24e08335Restoring Neuroprotective Tryptophan Metabolism via Targeted Probiotic Engineeri0.610.30TDCproposed2026-04-03SDA-2026-04-01-gap-20260401-225149
h-50a535f9SIRT6-NAD+ Axis Enhancement Therapy0.610.30SIRT6debated2026-04-02sda-2026-04-01-gap-v2-bc5f270e
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