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Hypotheses

2,342 items
IdTitleComposite ScoreConfidence ScoreTarget GeneStatusCreated AtAnalysis Id
h-a6e77292SGMS1-Driven Sphingomyelin Accumulation Impairs BACE1 Lysosomal Degradation via 0.730.72SGMS1, BECN1promoted2026-04-15SDA-2026-04-15-gap-pubmed-20260411-083737-59771b32
h-1a4820f3Seed-Proximal Asymmetric Duplex Stability Confers lncRNA-0021/miR-6361 Binding S0.730.30miR-6361 seed-proximal binding site (lncRNA-0021 coordinatesproposed2026-04-17SDA-2026-04-16-gap-pubmed-20260410-150509-76c40dac
hyp-lyso-snca-548064SNCA Oligomer Binding to LAMP2A Cytosolic Tail Prevents TorsinA-Mediated LAMP2A 0.730.62LAMP2active2026-04-28SRB-2026-04-29-hyp-lyso-snca-54
h-c8ccbee8Aquaporin-4 Polarization Rescue0.730.68AQP4debated2026-04-02sda-2026-04-01-gap-005
h-796cfd1cSMPD1 (Acid Sphingomyelinase) Inhibition for Ceramide Reduction and BACE1 Regula0.730.75SMPD1promoted2026-04-16SDA-2026-04-15-gap-debate-20260410-112819-e40e0fa2
h-bb518928Senescence-Associated Myelin Lipid Remodeling0.730.30PLA2G6/PLA2G4Adebated2026-04-02sda-2026-04-01-gap-013
h-var-f354525002Selective Neutral Sphingomyelinase-2 Inhibition Therapy0.730.30SMPD3promoted2026-04-12SDA-2026-04-01-gap-lipid-rafts-2026-04-01
h-7957bb2aSenescence-Induced Lipid Peroxidation Spreading0.730.40GPX4/SLC7A11debated2026-04-02sda-2026-04-01-gap-013
h-a0269f3c81G2019S Acts as Lysosomal Volume-Sensing Amplifier via Enhanced RAB29-Dependent R0.730.72LRRK2,RAB29proposed2026-04-26SDA-2026-04-23-gap-debate-20260417-033119-54941818
h-083d94e34bMetabolic-Support Secretome Dysfunction0.730.75HIF1A; SLC16A2 (MCT2); LDHAproposed2026-04-26SDA-2026-04-26-gap-pubmed-20260410-170057-a2f72fd8-debate
h-8254c04dfdEndosomal trafficking defects are the common upstream lesion linking APP process0.730.25SORL1, BIN1, PICALM, VPS35, APP, NTRK1proposed2026-04-25SDA-2026-04-25-gapdebate-e849205bca
h-26353f7f59Temporal order is subtype-specific rather than universal0.730.76APOE, SORL1, NTRK1, BIN1, PICALMproposed2026-04-25SDA-2026-04-25-gapdebate-e849205bca
h-08ca25f232H1: T-Type Calcium Channel–Driven Calcium Overload and Proteostasis Collapse0.730.72CACNA1H (Cav3.2), CAPN2, PPP2R2Dproposed2026-04-22SDA-2026-04-02-gap-ec-layer2-vulnerability
h-9c5abf9343Ubiquitin-Mediated Liquid-to-Solid Transition Prevention0.730.78G3BP1proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041423-2d1db50c
h-41bc2d38Adenosine-Astrocyte Metabolic Reset0.730.65ADORA2Apromoted2026-04-02sda-2026-04-01-gap-v2-18cf98ca
h-ec731b7aPhase-Separated Organelle Targeting0.730.80G3BP1debated2026-04-02sda-2026-04-01-gap-009
h-6ea2dc4c96SCFA Deficiency Drives Microglial Hyperactivation via GPR43/NF-κB Dysregulation0.730.82GPR43 (FFAR2), GPR41 (FFAR3), HDAC3, RELA (NF-κB p65)debated2026-04-26SDA-2026-04-26-gap-20260425-225305
h-54c6dd37ceTFEB/TFE3 Parallel Activation Drives Coordinated Organelle Clearance via CLEAR N0.730.70TFEB (TFEB), TFE3 (TFE3), mTORC1 (MTOR)proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062132-e71b3ef7
h-84808267Synthetic Biology BBB Endothelial Cell Reprogramming0.730.60TFR1, LRP1, CAV1, ABCB1debated2026-04-02sda-2026-04-01-gap-008
h-a1b56d74Metabolic Switch Targeting for A1→A2 Repolarization0.730.55HK2debated2026-04-02sda-2026-04-01-gap-007
h-3616325aMicroglial TREM2-Complement Axis Modulation0.730.80TREM2 and C3promoted2026-04-04SDA-2026-04-03-gap-seaad-v2-20260402032945
h-98b431baTFAM overexpression creates mitochondrial donor-recipient gradients for directed0.730.60TFAMdebated2026-04-02sda-2026-04-01-gap-v2-89432b95
h-8fe389e8Astrocyte-Mediated Neuronal Epigenetic Rescue0.730.65HDACdebated2026-04-02SDA-2026-04-04-gap-epigenetic-reprog-b685190e
h-SDA-2026-04-26-gapCalcium-Dependent S100B Release from Astrocyte End-Feet as an Early Signal of As0.720.49S100B (S100 Calcium Binding Protein B)proposed2026-04-26SDA-2026-04-26-gap-debate-20260426-011448-7c85f5dc
h-6f6c9d3cTDP-43 condensation thermodynamics as a therapeutic target and biomarker for nuc0.720.72TARDBP (TDP-43 protein); IPO4/IP09 (nuclear import receptorsproposed2026-04-26SDA-2026-04-10-gap-debate-20260410-075000-7396040a
h-5d943bfcProteostasis Enhancement via APOE Chaperone Targeting0.720.65HSPA1Aproposed2026-04-03sda-2026-04-01-gap-auto-fd6b1635d9
h-b9f5438cTBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimination Through Type I 0.720.60TBK1proposed2026-04-14SDA-2026-04-13-gap-pubmed-20260410-165527-8256a071
h-8a244611Context-Dependent Cx43 Modulation Based on Disease Stage0.720.52GJA1 (Cx43) - context-dependentpromoted2026-04-13SDA-2026-04-12-gap-debate-20260410-113038-57244485
h-25ec762b3fCSF YKL-40 as a Priming-Specific Chitinase Marker0.720.72CHI3L1/YKL-40proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062039-3b945972
h-99b4e2d2Interfacial Lipid Mimetics to Disrupt Domain Interaction0.720.68APOEdebated2026-04-02sda-2026-04-01-gap-010
h-5706bbd7Circadian Rhythm Entrainment of Reactive Astrocytes0.720.50BMAL1debated2026-04-02sda-2026-04-01-gap-007
h-1eaa052225Regional TREM2-Dependent Lipid Metabolism Determines Cortical Vulnerability in A0.720.30TREM2proposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041439-ec89b1e4
h-8d270062Sleep Spindle-Synaptic Plasticity Enhancement0.720.45CACNA1Gdebated2026-04-02sda-2026-04-01-gap-v2-18cf98ca
h-a1552ac3LXRβ-Selective Agonism as a Precision Therapeutic for APOE4-Driven Myelin Defici0.720.72NR1H2 (LXRβ)promoted2026-04-15SDA-2026-04-14-gap-pubmed-20260410-193244-89904941
h-056cb87f4eNLRP3 Inflammasome Inhibition for Neuroprotection in Parkinson's Disease0.720.72NLRP3proposed2026-04-29SDA-2026-04-28-gap-test-20260425-224949
h-b76cedd571Microglia-Mediated Neuroinflammation as a Disease-Amplifying Mechanism0.720.72NLRP3, TREM2, TYROBP, CX3CR1proposed2026-04-28SDA-2026-04-28-cross-disease-synthesis
h-72c719461cC9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD0.720.88C9orf72proposed2026-04-26test-hypothesis-fixtures-v1
h-51302631b4APOE4-driven pericyte injury/senescence is an upstream driver of early BBB break0.720.78APOE4, LRP1, PPIA, MMP9, PDGFRBproposed2026-04-25SDA-2026-04-25-gapdebate-de5dfc4391
h-90b7b77f59Bacterial Curli Amyloid → Nucleation of α-Synuclein Misfolding in Enteric Neuron0.720.72CsgA, CsgB, CsgC, α-synuclein (SNCA)proposed2026-04-22sda-2026-04-01-gap-20260401-225155
h-a5bc82c685Excessive C1q/C3/CR3 complement cascade activation initiates pre-symptomatic syn0.720.72C1QA, C1QB, C1QC, C3, ITGAM/ITGAXproposed2026-04-22SDA-2026-04-02-gap-synaptic-pruning-microglia
h-9ff41c2036H6: Layer II–Specific Loss of NPTX2 and Aberrant AMPAR Trafficking0.720.75NPTX2, ARCproposed2026-04-22SDA-2026-04-02-gap-ec-layer2-vulnerability
h-c410043ac4Antisense Oligonucleotide-Mediated APOE4 Haploinsufficiency0.720.75APOEproposed2026-04-22SDA-2026-04-02-gap-apoe4-targeting
h-a352af801cSASP Secretome-based Molecular Distinction via CXCL1/CXCL2/MMP-3 Ratio0.720.75CXCL1, CXCL2, MMP3proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062101-6af4ba5f
h-7af6de6f2aNLRP3 Inflammasome Lock Perpetuates Senescence-Associated Inflammasome Phenotype0.720.72NLRP3/CASP1/IL1Bproposed2026-04-22SDA-2026-04-06-gap-pubmed-20260406-041439-5f43216e
h-641ea3f1a7H3: APOE4 Impairs Cholesterol Trafficking, Triggering Astrocyte Senescence0.720.72ABCA1/ABCG1; LXR (NR1H3)proposed2026-04-22SDA-2026-04-06-gap-debate-20260406-062101-5d7b9dc0
h-5258e4d0eeAutophagic Receptor Sequestration via K63-Ub 'Signalone' Recognition0.720.25G3BP1proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-041423-2d1db50c
h-fca0433042Microglial IFN-β Priming of Motor Neuron cGAS/STING Amplification0.720.70IFNAR1/IFNAR2, STING (TMEM173), cGAS (CGAS)proposed2026-04-21SDA-2026-04-07-gap-pubmed-20260406-062141-611cf046
h-d4e73cf08fVCP/p97 ATPase mutations impair extraction of ubiquitinated autophagy substrates0.720.72VCPproposed2026-04-21SDA-2026-04-08-gap-pubmed-20260406-062212-6777e5dd
SDA-2026-04-16-hyp-eMetabolic Reprogramming to Reverse Senescence0.720.79SIRT1,PGC1A,NAMPTpromoted2026-04-16SDA-2026-04-04-gap-senescent-clearance-neuro
h-6756097bASO-Mediated Exon Skipping to Restore FUS-TAZ Chaperone Axis0.720.68FUSpromoted2026-04-15SDA-2026-04-14-gap-pubmed-20260410-184155-2ff305ca
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