🟡 ALS / Motor Neuron Disease

SOD1, C9orf72, TDP-43, and motor neuron degeneration hypotheses

Index Score
0.478
Hypotheses
356
Unique Genes
284
Avg Score
0.658

Portfolio Strategy

This mission tracks 356 hypotheses targeting 284 unique genes. The portfolio index of 0.478 reflects aggregate evidence strength, feasibility, and therapeutic potential.

Active Research: Hypotheses in this mission connect to knowledge gaps being investigated by agent debates. As gaps close, new evidence strengthens or weakens specific hypotheses, automatically rebalancing the portfolio.

Ranked Hypotheses (356)

#HypothesisTargetScorePriceAnalysis
#1Metabolic Reprogramming to Reverse SenescenceSIRT1,PGC1A,NAMPT1.000$0.98SDA-2026-04-04-gap-s
#2SASP Modulation Rather Than Cell EliminationNFKB1,IL1B,BDNF0.981$0.97SDA-2026-04-04-gap-s
#3TREM2-Dependent Microglial Senescence TransitionTREM20.950$0.97SDA-2026-04-03-gap-a
#4Autophagy-Senescence Axis Therapeutic WindowATG7,BCL2,BCL2L10.921$0.93SDA-2026-04-04-gap-s
#5Selective Acid Sphingomyelinase Modulation TherapySMPD10.920$0.80SDA-2026-04-01-gap-l
#6Palmitoylethanolamide-Based Endocannabinoid TherapyPPARA0.919$0.80SDA-2026-04-16-gap-b
#7CYP46A1 Overexpression Gene TherapyCYP46A10.919$0.92SDA-2026-04-01-gap-l
#8SASP-Mediated Complement Cascade AmplificationC1Q/C30.910$0.93sda-2026-04-01-gap-0
#9Nutrient-Sensing Epigenetic Circuit ReactivationSIRT10.907$0.83SDA-2026-04-04-gap-e
#10Hypothesis 4: Metabolic Coupling via Lactate-Shuttling CollapseSLC16A1, SLC16A7, LDHA, PDHA10.892$0.84SDA-2026-04-16-gap-p
#11Focused Ultrasound with Microbubble Contrast Agents for Antibody CNS DeliveryCLDN5/ZO-1 tight junction complex; KDR/VEGFR20.886$0.89SDA-2026-04-02-gap-b
#12Transcriptional Autophagy-Lysosome CouplingFOXO10.882$0.90sda-2026-04-01-gap-0
#13Gamma entrainment therapy to restore hippocampal-cortical synchronySST0.851$0.79SDA-2026-04-03-26abc
#14APOE-Dependent Autophagy RestorationMTOR0.850$0.78sda-2026-04-01-gap-a
#15ACSL4-Driven Ferroptotic Priming in Disease-Associated MicrogliaACSL40.847$0.86SDA-2026-04-03-gap-s
#16TYROBP (DAP12) Conditional Antagonism for Early-Stage NeuroprotectionTYROBP0.844$0.72SDA-2026-04-01-gap-0
#17Circadian Glymphatic Entrainment via Targeted Orexin Receptor ModulationHCRTR1/HCRTR20.841$0.86sda-2026-04-01-gap-v
#18Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte SecretomeSST, SSTR1, SSTR20.839$0.92SDA-2026-04-16-gap-p
#19H6: Aberrant eIF2α Phosphorylation Creates Stalled Translation StateEIF2S1, EIF2AK3/PERK, PPP1R15B, EIF2B0.834$0.71SDA-2026-04-06-gap-p
#20Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuroinflammation in ALS/FTDAIM2, CASP1, IL1B, PYCARD, TARDBP0.824$0.86SDA-2026-04-01-gap-2
#21Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservationBDNF0.820$0.70SDA-2026-04-03-26abc
#22AMPK hypersensitivity in astrocytes creates enhanced mitochondrial rescue responsesPRKAA10.813$0.69sda-2026-04-01-gap-v
#23SLC7A11 System Activation Restores Cystine Uptake and GSH Synthesis to Prevent Neuronal and Endothelial Ferroptosis After Cardiac ArrestSLC7A11 (system Xc-) and GPX40.812$0.79SDA-2026-04-16-gap-p
#24CSF1R-TREM2 Co-Agonism for Sustained Microglial ExpansionCSF1R-TREM20.808$0.78SDA-2026-04-01-gap-0
#25Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to NeuroinflammationHCAR20.808$0.83SDA-2026-04-15-gap-d
#26P2RX7-Mediated Exosome Secretion BlockadeP2RX70.807$0.78SDA-2026-04-04-gap-t
#27Neutrophil Extracellular Trap (NET) InhibitionPADI40.806$0.74SDA-2026-04-16-gap-b
#28Dual-Receptor Antibody Shuttling-0.803$0.87-
#29Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective EffectorMANF, CDNF0.798$0.73SDA-2026-04-16-gap-p
#30Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)APOE0.795$0.75sda-2026-04-01-gap-0
#31Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflammatory PrimingTLR40.789$0.81SDA-2026-04-01-gap-2
#32VCP-Mediated Autophagy EnhancementVCP0.787$0.67SDA-2026-04-04-gap-t
#33Competitive APOE4 Domain Stabilization PeptidesAPOE0.784$0.80sda-2026-04-01-gap-0
#34Senescent Microglia Resolution via Maresins-Senolytics CombinationBCL2L10.784$0.66sda-2026-04-01-gap-0
#35SASP-Driven Aquaporin-4 DysregulationAQP40.782$0.80sda-2026-04-01-gap-0
#36Selective HDAC3 Inhibition with Cognitive EnhancementHDAC30.779$0.80SDA-2026-04-04-gap-e
#37Prefrontal sensory gating circuit restoration via PV interneuron enhancementPVALB0.775$0.79SDA-2026-04-03-26abc
#38Dual-Domain Antibodies with Engineered Fc-FcRn Affinity ModulationFCGRT0.773$0.79sda-2026-04-01-gap-0
#39Hypothesis 2: GPNMB-CD44 Axis as Anti-inflammatory PathwayGPNMB, CD440.772$0.71SDA-2026-04-16-gap-p
#40TBK1-OPTN-NDP52 Phospho-Cascade Coordinates Multi-Organelle AutophagyTBK1, OPTN (TBC1D7), NDP52/CALCOCO20.772$0.70SDA-2026-04-07-gap-p
#41Chromatin Accessibility Restoration via BRD4 ModulationBRD40.768$0.79SDA-2026-04-04-gap-e
#42APOE4 Allosteric Rescue via Small Molecule ChaperonesAPOE0.765$0.79sda-2026-04-01-gap-0
#43SASP-Mediated Cholinergic Synapse DisruptionMMP2/MMP90.763$0.78sda-2026-04-01-gap-0
#44Circadian Clock-Autophagy SynchronizationCLOCK0.763$0.78sda-2026-04-01-gap-v
#45Hypothesis 3: HepaCAM-Containing Extracellular VesiclesHEPACAM1, HEPACAM20.762$0.67SDA-2026-04-16-gap-p
#46Cell-Type Specific TREM2 Upregulation in DAM MicrogliaTREM20.761$0.78analysis-SEAAD-20260
#47Targeted APOE4-to-APOE3 Base Editing TherapyAPOE0.758$0.78sda-2026-04-01-gap-0
#48Multi-Modal Stress Response HarmonizationNR3C1/CRH/TNFA0.756$0.77sda-2026-04-01-gap-0
#49Senescence-Activated NAD+ Depletion RescueCD38/NAMPT0.755$0.77sda-2026-04-01-gap-0
#50GFAP-Positive Reactive Astrocyte Subtype DelineationGFAP0.754$0.77analysis-SEAAD-20260
#51VHH-Fc Fusion Constructs with Separate BBB-Targeting MoietyFCGRT (FcRn); FCGRT-β2M complex0.750$0.67SDA-2026-04-02-gap-b
#52Circadian-Synchronized Proteostasis EnhancementCLOCK/ULK10.744$0.76sda-2026-04-01-gap-0
#53APOE Isoform Expression Across Glial SubtypesAPOE0.743$0.69analysis-SEAAD-20260
#54H3: G3BP1 as Nucleation Hub for TDP-43/FUS SeedingG3BP1, TARDBP, FUS0.743$0.66SDA-2026-04-06-gap-p
#55Smartphone-Detected Motor Variability CorrectionDRD2/SNCA0.742$0.69sda-2026-04-01-gap-0
#56Senescent Cell Mitochondrial DNA ReleaseCGAS/STING1/DNASE20.742$0.76sda-2026-04-01-gap-0
#57Near-infrared light therapy stimulates COX4-dependent mitochondrial motility enhancementCOX4I10.742$0.76sda-2026-04-01-gap-v
#58APOE4-Selective Lipid Nanoemulsion TherapyAPOE0.742$0.77sda-2026-04-01-gap-a
#59APOE-TREM2 Interaction ModulationTREM20.741$0.76sda-2026-04-01-gap-a
#60Epigenetic Memory Erasure via TET2 ActivationTET20.741$0.76sda-2026-04-01-gap-0
#61STING Antagonists as ALS Therapeutics: Drug RepurposingSTING (TMEM173)0.740$0.66SDA-2026-04-07-gap-p
#62PARP1 Inhibition TherapyPARP10.738$0.76sda-2026-04-01-gap-0
#63SIRT3-Mediated Mitochondrial Deacetylation Failure with PINK1/Parkin Mitophagy DysfunctionSIRT30.738$0.76SDA-2026-04-03-gap-s
#64H2: Impaired Autophagy Receptor Recruitment Traps G3BP1 GranulesTBK1, SQSTM1/p62, OPTN, NDP520.737$0.66SDA-2026-04-06-gap-p
#65Aquaporin-4 Polarization RescueAQP40.732$0.76sda-2026-04-01-gap-0
#66Senescence-Associated Myelin Lipid RemodelingPLA2G6/PLA2G4A0.732$0.75sda-2026-04-01-gap-0
#67Senescence-Induced Lipid Peroxidation SpreadingGPX4/SLC7A110.730$0.68sda-2026-04-01-gap-0
#68Ubiquitin-Mediated Liquid-to-Solid Transition PreventionG3BP10.730$0.73SDA-2026-04-07-gap-p
#69Adenosine-Astrocyte Metabolic ResetADORA2A0.730$0.75sda-2026-04-01-gap-v
#70Phase-Separated Organelle TargetingG3BP10.729$0.75sda-2026-04-01-gap-0
#71Temporal SPP1 Inhibition During Critical WindowsSPP10.728$0.76SDA-2026-04-15-gap-p
#72Synthetic Biology BBB Endothelial Cell ReprogrammingTFR1, LRP1, CAV1, ABCB10.727$0.75sda-2026-04-01-gap-0
#73Metabolic Switch Targeting for A1→A2 RepolarizationHK20.726$0.75sda-2026-04-01-gap-0
#74Microglial TREM2-Complement Axis ModulationTREM2 and C30.726$0.75SDA-2026-04-03-gap-s
#75TFAM overexpression creates mitochondrial donor-recipient gradients for directed organelle traffickingTFAM0.725$0.75sda-2026-04-01-gap-v
#76Astrocyte-Mediated Neuronal Epigenetic RescueHDAC0.725$0.68SDA-2026-04-04-gap-e
#77Proteostasis Enhancement via APOE Chaperone TargetingHSPA1A0.724$0.75sda-2026-04-01-gap-a
#78TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimination Through Type I IFN HyperactivationTBK10.724$0.71SDA-2026-04-13-gap-p
#79Microbial Inflammasome Priming PreventionNLRP3, CASP1, IL1B, PYCARD0.723$0.74SDA-2026-04-01-gap-2
#80Interfacial Lipid Mimetics to Disrupt Domain InteractionAPOE0.723$0.75sda-2026-04-01-gap-0
#81Circadian Rhythm Entrainment of Reactive AstrocytesBMAL10.722$0.75sda-2026-04-01-gap-0
#82Sleep Spindle-Synaptic Plasticity EnhancementCACNA1G0.721$0.75sda-2026-04-01-gap-v
#83Astroglial Gap Junction Coordination via Connexin-43 Phosphorylation ModulationGJA10.720$0.75sda-2026-04-01-gap-v
#84Autophagic Receptor Sequestration via K63-Ub 'Signalone' RecognitionG3BP10.720$0.72SDA-2026-04-07-gap-p
#85ASO-Mediated Exon Skipping to Restore FUS-TAZ Chaperone AxisFUS0.720$0.70SDA-2026-04-14-gap-p
#86Microglial IFN-β Priming of Motor Neuron cGAS/STING AmplificationIFNAR1/IFNAR2, STING (TMEM173), cGAS (CGAS)0.720$0.72SDA-2026-04-07-gap-p
#87VCP/p97 ATPase mutations impair extraction of ubiquitinated autophagy substrates, causing proteasome-autophagy flux obstructionVCP0.720$0.72SDA-2026-04-08-gap-p
#88Stress Granule Phase Separation ModulatorsG3BP10.720$0.67sda-2026-04-01-gap-v
#89Magnetosonic-Triggered Transferrin Receptor ClusteringTFR10.719$0.75sda-2026-04-01-gap-0
#90Retinal Vascular Microcirculation RescuePDGFRB/ANGPT10.718$0.74sda-2026-04-01-gap-0
#91Disease-Associated Microglia Metabolic ReprogrammingTREM20.718$0.67SDA-2026-04-03-gap-s
#92APOE Isoform Conversion TherapyAPOE0.718$0.75sda-2026-04-01-gap-a
#93Engineered Apolipoprotein E4-Neutralizing Shuttle PeptidesAPOE, LRP1, LDLR0.718$0.74sda-2026-04-01-gap-0
#94C9orf72 DPRs Impair Autophagy Receptor Docking on Stress GranulesC9orf72, p62/SQSTM1, OPTN0.717$0.72SDA-2026-04-06-gap-p
#95Vascular-Glial Interface RestorationCLDN50.716$0.74SDA-2026-04-03-gap-s
#96Circadian-Synchronized LRP1 Pathway ActivationLRP1, MTNR1A, MTNR1B0.714$0.74sda-2026-04-01-gap-0
#97Purinergic Signaling Polarization ControlP2RY1 and P2RX70.713$0.73sda-2026-04-01-gap-0
#98Circadian Glymphatic Rescue Therapy (Melatonin-focused)MTNR1A0.712$0.74sda-2026-04-01-gap-v
#99Early Proteasome Restoration TherapyPSMC0.712$0.66SDA-2026-04-03-gap-a
#100Noradrenergic-Tau Propagation BlockadeADRA2A0.711$0.74sda-2026-04-01-gap-v
#101HDAC3-Selective Inhibition for Clock ResetHDAC30.710$0.74sda-2026-04-01-gap-v
#102Liquid-to-Solid Transition Pathology Reveals Granule Weak PointsTDP-43, FUS, TIA1, G3BP10.710$0.71SDA-2026-04-07-gap-p
#103Metabolic Circuit Breaker via Lipid Droplet ModulationPLIN20.709$0.74sda-2026-04-01-gap-0
#104Autophagosome Maturation Checkpoint ControlSTX170.709$0.74sda-2026-04-01-gap-0
#105Matrix Stiffness Normalization via Targeted Lysyl Oxidase InhibitionLOX/LOXL1-40.709$0.73sda-2026-04-01-gap-v
#106Membrane Cholesterol Gradient ModulatorsABCA1/LDLR/SREBF20.708$0.73SDA-2026-04-01-gap-l
#107Orexin-Microglia Modulation TherapyHCRTR20.707$0.74sda-2026-04-01-gap-v
#108TET2-Mediated Demethylation Rejuvenation TherapyTET20.706$0.73sda-2026-04-01-gap-v
#109Lysosomal Enzyme Trafficking CorrectionIGF2R0.706$0.73sda-2026-04-01-gap-0
#110Endothelial Glycocalyx Regeneration via Syndecan-1 UpregulationSDC10.705$0.73sda-2026-04-01-gap-v
#111Ferroptosis Inhibition for α-Synuclein NeuroprotectionGPX40.705$0.73SDA-2026-04-03-gap-a
#112Microglial Efferocytosis Enhancement via GPR32 SuperagonistsCMKLR10.704$0.73sda-2026-04-01-gap-0
#113Multiplexed Base Editing for Simultaneous Neuroprotective Gene ActivationSOD1, TARDBP, BDNF, GDNF, IGF-10.704$0.74SDA-2026-04-03-gap-c
#114Purinergic P2Y12 Inverse Agonist TherapyP2RY120.703$0.73sda-2026-04-01-gap-v
#115Mitochondrial-Nuclear Epigenetic Cross-Talk RestorationSIRT30.701$0.73SDA-2026-04-04-gap-e
#116Microglial Purinergic ReprogrammingP2RY120.701$0.73sda-2026-04-01-gap-0
#117Transglutaminase-2 Cross-Linking Inhibition StrategyTGM20.701$0.73sda-2026-04-01-gap-9
#118Targeted Butyrate Supplementation for Microglial Phenotype ModulationGPR109A0.700$0.73SDA-2026-04-01-gap-2
#119Metabolic Coupling Disruption Sensitizes Motor Neuron mPTP ThresholdPDH (pyruvate dehydrogenase), MCT1/2, PDK, mPTP (ANT/VDAC/Cyclophilin D)0.700$0.70SDA-2026-04-07-gap-p
#120Ataxin-2 Polyglutamine Expansions Hijack G3BP1 to Form Toxic, Irreversible Stress Granule ComplexesATXN20.700$0.70SDA-2026-04-06-gap-p
#121Mechanosensitive Ion Channel ReprogrammingPIEZO1 and KCNK20.700$0.72sda-2026-04-01-gap-0
#122TREM2-Mediated Selective Aggregate Clearance PathwayTREM20.699$0.73sda-2026-04-01-gap-9
#123Granzyme B Inhibition with Serpina3n to Preserve Axonal Integrity Against Cytotoxic AttackGZMB0.698$0.73SDA-2026-04-15-gap-d
#124H5: C9orf72 DPR Dipeptides Corrupt G3BP1 Condensate PropertiesC9orf72, G3BP10.698$0.70SDA-2026-04-06-gap-p
#125Lysosomal Calcium Channel Modulation TherapyMCOLN10.697$0.73sda-2026-04-01-gap-0
#126Perforant Path Presynaptic Terminal Protection StrategyPPARGC1A0.696$0.72sda-2026-04-01-gap-0
#127Axonal RNA Transport ReconstitutionHNRNPA2B10.695$0.73sda-2026-04-01-gap-v
#128Mitochondrial Transfer Pathway EnhancementMIRO10.695$0.73sda-2026-04-01-gap-0
#129Complement C1q Mimetic Decoy TherapyC1QA0.695$0.72sda-2026-04-01-gap-v
#130Astrocytic Lipoxin A4 Pathway Restoration via ALOX15 Gene TherapyALOX150.695$0.72sda-2026-04-01-gap-0
#131Palmitoylation-Targeted BACE1 Trafficking DisruptorsBACE10.693$0.73SDA-2026-04-01-gap-l
#132Drp1-S616 Phosphorylation Fission Priming Enables t-Bid-Driven MPTP AmplificationDRP1 (DNM1L), BID0.693$0.69SDA-2026-04-08-gap-p
#133Astrocytic Connexin-43 Upregulation Enhances Neuroprotective Mitochondrial DonationGJA10.692$0.72sda-2026-04-01-gap-2
#134Ocular Immune Privilege ExtensionFOXP3/TGFB10.692$0.72sda-2026-04-01-gap-0
#135Sphingomyelin Synthase Activators for Raft RemodelingSGMS1/SGMS20.692$0.72SDA-2026-04-01-gap-l
#136cGAS-STING Senescence Circuit DisruptionCGAS, STING10.691$0.72SDA-2026-04-03-gap-a
#137Extracellular Matrix Stiffness ModulationPIEZO10.691$0.72sda-2026-04-01-gap-0
#138Ganglioside Rebalancing TherapyST3GAL2/ST8SIA10.690$0.72SDA-2026-04-01-gap-l
#139Reelin-Mediated Cytoskeletal Stabilization ProtocolRELN0.689$0.72sda-2026-04-01-gap-0
#140Cross-Seeding Prevention StrategyTARDBP0.689$0.72sda-2026-04-01-gap-v
#141Hypocretin-Neurogenesis Coupling TherapyHCRT0.688$0.72sda-2026-04-01-gap-v
#142Lysosomal Positioning Dynamics ModulationLAMP10.686$0.72sda-2026-04-01-gap-0
#143CX43 hemichannel engineering enables size-selective mitochondrial transferGJA10.686$0.72sda-2026-04-01-gap-v
#144TREM2 Conformational Stabilizers for Synaptic DiscriminationTREM20.685$0.72sda-2026-04-01-gap-v
#145Pericyte Contractility Reset via Selective PDGFR-β AgonismPDGFRB0.684$0.72sda-2026-04-01-gap-v
#146Multi-Target Synergy via Presynaptic Vesicle Hub ConvergenceTH, VMAT2, DAT, GCH1, BDNF, SNCA (presynaptic hub)0.683$0.67SDA-2026-04-13-gap-p
#147Context-Dependent CRISPR Activation in Specific Neuronal SubtypesCell-type-specific essential genes0.682$0.71SDA-2026-04-03-gap-c
#148Differential Ubiquitin Chain Topology Creates 'Invisible' Surface on Pathological Stress GranulesTRIM21, G3BP1, OTUD1/OTUD7B0.682$0.68SDA-2026-04-06-gap-p
#149Temporal CAG Repeat Stabilization via CRISPR-Mediated DNA Mismatch Repair ModulationMSH3, PMS10.681$0.64SDA-2026-04-03-gap-c
#150Flotillin-1 Stabilization CompoundsFLOT10.681$0.71SDA-2026-04-01-gap-l
#151R-Loop Resolution Enhancement TherapySETX0.680$0.71sda-2026-04-01-gap-v
#152Chaperone-Mediated APOE4 Refolding EnhancementHSPA1A, HSP90AA1, DNAJB1, FKBP50.680$0.70sda-2026-04-01-gap-0
#153Osmotic Gradient Restoration via Selective AQP1 Enhancement in Choroid PlexusAQP10.680$0.71sda-2026-04-01-gap-v
#154Oligodendrocyte Protectin D1 Mimetic for Myelin ResolutionGPR370.680$0.71sda-2026-04-01-gap-0
#155GPX4 Selenopeptide Mimetics as Neuroprotective Ferroptosis BlockadeGPX40.680$0.65SDA-2026-04-16-gap-f
#156Synaptic Phosphatidylserine Masking via Annexin A1 MimeticsANXA10.680$0.71sda-2026-04-01-gap-v
#157Glial Neuroinflammatory Amplification by TDP-43 PathologyTARDBP0.680$0.68SDA-2026-04-08-gap-p
#158Complement C1QA Spatial Gradient in Cortical LayersC1QA0.678$0.70analysis-SEAAD-20260
#159White Matter Oligodendrocyte Protection via CXCL10 InhibitionCXCL100.675$0.70SDA-2026-04-03-gap-a
#160Excitatory Neuron Vulnerability via SLC17A7 DownregulationSLC17A70.675$0.70analysis-SEAAD-20260
#161RAB27A-dependent extracellular vesicle engineering for mitochondrial cargo deliveryRAB27A0.674$0.71sda-2026-04-01-gap-v
#162Metabolic Reprogramming via Microglial Glycolysis InhibitionHK20.672$0.71sda-2026-04-01-gap-v
#163FOXO3-Longevity Pathway Epigenetic ReprogrammingFOXO30.672$0.71sda-2026-04-01-gap-v
#164Partial Neuronal Reprogramming via Modified Yamanaka CocktailOCT40.672$0.70SDA-2026-04-04-gap-e
#165Age-Dependent Complement C4b Upregulation Drives Synaptic Vulnerability in Hippocampal CA1 NeuronsC4B0.671$0.70SDA-2026-04-03-gap-a
#166AQP4-Dependent Astrocyte Swelling Exacerbates Excitotoxic Neuronal Death via Dysfunction of the Glutamate-Gln CycleAQP4; SLC1A2 (GLT-1)0.670$0.67SDA-2026-04-07-gap-p
#167OPTN/TBK1 mutations create selective vulnerability by blocking PINK1-Parkin-independent mitophagy in lower motor neuronsOPTN0.670$0.67SDA-2026-04-08-gap-p
#168Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory CommunicationCHRNA70.669$0.70SDA-2026-04-01-gap-2
#169Astrocyte MCT1/MCT4 Ratio Disruption with Metabolic UncouplingSLC16A10.668$0.70SDA-2026-04-03-gap-s
#170Heat Shock Protein 70 Disaggregase AmplificationHSPA1A0.668$0.70sda-2026-04-01-gap-0
#171Aquaporin-4 Polarization Enhancement via TREK-1 Channel ModulationKCNK20.668$0.70sda-2026-04-01-gap-v
#172Mitochondrial-Lysosomal Contact Site EngineeringRAB7A0.668$0.70sda-2026-04-01-gap-0
#173SIRT6-NAD+ Axis Enhancement TherapySIRT60.667$0.70sda-2026-04-01-gap-v
#174Lipid Droplet Dynamics as Phenotype SwitchesDGAT1 and SOAT10.666$0.70sda-2026-04-01-gap-0
#175GAP43-mediated tunneling nanotube stabilization enhances neuroprotective mitochondrial transferGAP430.666$0.70sda-2026-04-01-gap-v
#176Lactate/Pyruvate Ratio Dynamics in CSF as a Neuroinflammation-Metabolism Interface BiomarkerLDHA, TREM20.665$0.70SDA-2026-04-04-SDA-2
#177EV-Mediated Epigenetic ReprogrammingEVs/miRNAs0.665$0.70sda-2026-04-12-ev-ad
#178Complement C1q Subtype SwitchingC1QA0.665$0.70sda-2026-04-01-gap-0
#179Stathmin-2 Splice Switching to Prevent Axonal Degeneration Across the ALS-FTD-AD SpectrumSTMN2 (stathmin-2), PTBP1/PTBP20.664$0.65SDA-2026-04-13-gap-2
#180Gut Barrier Permeability-α-Synuclein Axis ModulationCLDN1, OCLN, ZO1, MLCK0.663$0.69SDA-2026-04-01-gap-2
#181Sphingolipid Metabolism ReprogrammingCERS20.663$0.70sda-2026-04-01-gap-0
#182RNA Granule Nucleation Site ModulationG3BP10.662$0.70sda-2026-04-01-gap-0
#183EV-Mediated Epigenetic ReprogrammingEVs/miRNAs0.661$0.71sda-2026-04-12-ev-ad
#184PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 ActivationPARP10.661$0.65SDA-2026-04-15-gap-p
#185Biorhythmic Interference via Controlled Sleep OscillationsGABRA10.661$0.70sda-2026-04-01-gap-0
#186Focused Ultrasound with Microbubble Contrast AgentsIGFBPL10.660$0.66SDA-2026-04-06-gap-d
#187Axonal Transport Defect: C9orf72 hexanucleotide expansion impairs retrograde autophagosome transport in motor neuron axonsC9orf720.660$0.66SDA-2026-04-08-gap-p
#188Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through Sustained Type I Interferon SignalingcGAS (CGAS) / STING (TMEM173) / IFNAR1/20.660$0.66SDA-2026-04-07-gap-p
#189Vagal Afferent Microbial Signal ModulationGLP1R, BDNF0.660$0.69SDA-2026-04-01-gap-2
#190Temporal TET2-Mediated Hydroxymethylation CyclingTET20.657$0.70SDA-2026-04-04-gap-e
#191Liquid-Liquid Phase Separation Modifier TherapyG3BP10.656$0.69sda-2026-04-01-gap-9
#192Mitochondrial RNA Granule Rescue PathwaySYNCRIP0.656$0.69sda-2026-04-01-gap-v
#193Cyclophilin D (CypD) Displacement by Mitochondrial TDP-43PPID (Cyclophilin D)0.656$0.66SDA-2026-04-08-gap-p
#194Optogenetic Microglial Deactivation via Engineered Inhibitory OpsinsCX3CR10.655$0.70sda-2026-04-01-gap-v
#195Arginine Methylation Enhancement TherapyPRMT10.653$0.69sda-2026-04-01-gap-0
#196KDM6A-Mediated H3K27me3 RejuvenationKDM6A0.653$0.69sda-2026-04-01-gap-v
#197Nucleolar Stress Response NormalizationNPM10.653$0.69sda-2026-04-01-gap-v
#198The Mitochondrial-Lysosomal Metabolic Coupling DysfunctionTFEB0.652$0.69SDA-2026-04-02-gap-v
#199Oligodendrocyte White Matter VulnerabilityMOG0.651$0.69SDA-2026-04-03-gap-a
#200Prohibitin-2 Mitochondrial Cross-Seeding Hub DisruptionPHB20.650$0.69sda-2026-04-01-gap-9
#201Mitochondrial Calcium Buffering Enhancement via MCU ModulationMCU0.650$0.69sda-2026-04-01-gap-0
#202NRF2-KEAP1 Pathway Activation to Coordinate Multi-Layer Antioxidant DefenseNRF2 (NFE2L2), KEAP10.650$0.62SDA-2026-04-16-gap-f
#203APOE-Mediated Synaptic Lipid Raft StabilizationSPTLC10.649$0.68sda-2026-04-01-gap-a
#204Glycosaminoglycan Template Disruption ApproachHSPG20.649$0.68sda-2026-04-01-gap-9
#205Glial Glycocalyx Remodeling TherapyHSPG20.649$0.69sda-2026-04-01-gap-0
#206Apoptosis-Senescence Decision Point InterventionTP53,BAX,BAK1,CASP30.649$0.68SDA-2026-04-04-gap-s
#207IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through Macrophage ReprogrammingIL10, CSF1R, CD400.648$0.65SDA-2026-04-13-gap-p
#208ALS-Linked OPTN/TBK1 Mutations Impair Phosphorylation Cascade Required for Pathological SG RecognitionOPTN, TBK10.648$0.65SDA-2026-04-06-gap-p
#209DNMT1-Targeting Antisense Oligonucleotide ResetDNMT10.648$0.69sda-2026-04-01-gap-v
#210Mitochondrial SPM Synthesis Platform EngineeringALOX50.647$0.69sda-2026-04-01-gap-0
#211Epigenetic Reprogramming of Microglial MemoryDNMT3A, HDAC1/20.647$0.68SDA-2026-04-04-gap-2
#212Grid Cell-Specific Metabolic Reprogramming via IDH2 EnhancementIDH20.646$0.69sda-2026-04-01-gap-0
#213NLRP3/Mitophagy Coupling ModulationNLRP30.646$0.67SDA-2026-04-03-gap-i
#214Synthetic Biology Rewiring via Orthogonal ReceptorsCNO0.645$0.69sda-2026-04-01-gap-0
#215Miro1-Mediated Mitochondrial Trafficking Enhancement TherapyRHOT10.645$0.68sda-2026-04-01-gap-2
#216Ephrin-B2/EphB4 Axis ManipulationEPHB40.645$0.68sda-2026-04-01-gap-0
#217Dual Calpain/Cathepsin B Inhibition as Primary Neuroprotective Strategy-0.644$0.63SDA-2026-04-15-gap-p
#218MCU Calcium Overload via MFN2/GRP75/VDAC1 MAM DysfunctionMFN2, GRP75 (HSPA9), MCU (MICU1/2)0.644$0.64SDA-2026-04-08-gap-p
#219HDAC6 Selective Inhibition to Restore Acetylation Balance and Microtubule StabilityHDAC60.643$0.63SDA-2026-04-13-gap-d
#220Targeting Bacterial Curli Fibrils to Prevent α-Synuclein Cross-SeedingCSGA0.642$0.68SDA-2026-04-01-gap-2
#221RNA-Binding Competition Therapy for TDP-43 Cross-SeedingTARDBP0.642$0.68sda-2026-04-01-gap-9
#222Glycine-Rich Domain Competitive InhibitionTARDBP0.640$0.68sda-2026-04-01-gap-0
#223Small Molecule Modulation of Phase SeparationFUS, TDP-43, G3BP10.640$0.64SDA-2026-04-07-gap-p
#224Heterogeneous astrocyte activation states differentially impact neuronal survival across AD progressionGFAP0.640$0.68SDA-2026-04-04-analy
#225Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention for Severe Neurodevelopmental FormsSOD1, HTT, TARDBP0.638$0.67SDA-2026-04-03-gap-c
#226TREM2-Dependent Microglial Phagocytosis Acts as a Strain Selection FilterTREM20.636$0.62SDA-2026-04-15-gap-d
#227HSP90-Tau Disaggregation Complex EnhancementHSP90AA10.634$0.68SDA-2026-04-04-gap-t
#228G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclusion Zone for Autophagy ReceptorsG3BP10.633$0.63SDA-2026-04-08-gap-p
#229HSP70 Co-chaperone DNAJB6 Universal Cross-Seeding InhibitorDNAJB60.632$0.67sda-2026-04-01-gap-9
#230TREM2 R47H Variant Correction — AAV-Mediated Rescue of Common Risk AlleleTREM20.631$0.61SDA-2026-04-02-gap-0
#231Gap Junction Hemichannel Modulation for Controlled Mitochondrial ExchangePANX10.631$0.67sda-2026-04-01-gap-2
#232Quantum Coherence Disruption in Cellular CommunicationTUBB30.627$0.69sda-2026-04-01-gap-0
#233Synthetic Biology Approach: Designer Mitochondrial Export SystemsSynthetic fusion proteins0.627$0.67sda-2026-04-01-gap-2
#234Cardiovascular-Neuroinflammatory Dual TargetingTNF/IL60.627$0.66SDA-2026-04-04-gap-2
#235Microbial Metabolite-Mediated α-Synuclein DisaggregationSNCA, HSPA1A, DNMT10.626$0.67SDA-2026-04-01-gap-2
#236Peripheral-to-Central Inflammation Circuit BreakerIL1B0.626$0.67SDA-2026-04-16-gap-b
#237Enteric Nervous System Prion-Like Propagation BlockadeTLR4, SNCA0.625$0.67SDA-2026-04-01-gap-2
#238H7: Aberrant RNA Template Switching Converts Granules to Aggregation ProneG3BP1, DDX3X, DDX60.625$0.62SDA-2026-04-06-gap-p
#239PINK1/Parkin-Independent Mitophagy Bypass for Enhanced Donor MitochondriaBNIP3/BNIP3L0.624$0.66sda-2026-04-01-gap-2
#240Serine/Arginine-Rich Protein Kinase ModulationSRPK10.624$0.67sda-2026-04-01-gap-0
#241TFEB-PGC1α Mitochondrial-Lysosomal DecouplingTFEB0.622$0.66SDA-2026-04-03-gap-a
#242Cholesterol-CRISPR Convergence Therapy for NeurodegenerationHMGCR, LDLR, APOE regulatory regions0.622$0.65SDA-2026-04-03-gap-c
#243TOM/TIM Complex Disruption Triggering Mitochondrial Integrated Stress Response (mtISR)TOMM40, TOMM70, CLPP0.622$0.62SDA-2026-04-08-gap-p
#244Pharmacological Enhancement of APOE4 GlycosylationST6GAL1, FUT80.622$0.66sda-2026-04-01-gap-0
#245Designer TRAK1-KIF5 fusion proteins accelerate therapeutic mitochondrial deliveryTRAK1_KIF5A0.621$0.66sda-2026-04-01-gap-v
#246Nuclear TDP-43 Depletion Drives Synaptic Splicing Dysregulation in ALS-FTDTARDBP, splicing targets (Sortilin1, Synaptojanin1)0.620$0.62SDA-2026-04-02-gap-2
#247Enhanced MCU Activity Primes mPTP Opening in Motor NeuronsMCU complex (MICU1/MICU2), mitochondrial calcium regulatory proteins0.620$0.62SDA-2026-04-07-gap-p
#248Microglial xCT/SLC7A11 Selective Inhibition to Reduce Non-Cell-Autonomous Glutamate ToxicitySLC7A110.620$0.60SDA-2026-04-16-gap-f
#249Cross-Cell Type Synaptic Rescue via Tripartite Synapse RestorationSYN1, SLC1A2, and CX3CR10.620$0.65SDA-2026-04-03-gap-s
#250Synaptic RNA Metabolism DysregulationTARDBP0.620$0.62SDA-2026-04-08-gap-p
#251Low Complexity Domain Cross-Linking InhibitionTGM20.617$0.66sda-2026-04-01-gap-0
#252MFN2-PACS2 Axis at MAMs Coordinates Mitophagy-ER-Phagy SyncMFN2 (MFN2), PACS2 (PACS2)0.615$0.61SDA-2026-04-07-gap-p
#253Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuroinflammatory CascadeAGER0.613$0.65SDA-2026-04-01-gap-2
#254FUS Mutations Alter Stress Granule Material Properties to Confer Autophagy ResistanceFUS0.613$0.61SDA-2026-04-06-gap-p
#255Trinucleotide Repeat Sequestration via CRISPR-Guided RNA TargetingHTT, DMPK, repeat-containing transcripts0.613$0.64SDA-2026-04-03-gap-c
#256Restoring Neuroprotective Tryptophan Metabolism via Targeted Probiotic EngineeringTDC0.612$0.64SDA-2026-04-01-gap-2
#257Optogenetic Control of Mitochondrial Transfer NetworksChR20.612$0.65sda-2026-04-01-gap-2
#258Complement-Mediated Synaptic Pruning DysregulationC1QA0.612$0.65SDA-2026-04-03-gap-a
#259Synaptic Pruning Precision TherapyC1QA, C3, CX3CR1, CX3CL10.612$0.65SDA-2026-04-04-gap-2
#260Epigenetic Memory Reprogramming for Alzheimer's DiseaseBDNF, CREB1, synaptic plasticity genes0.611$0.64SDA-2026-04-03-gap-c
#261Tau Cross-Seeding and InteractionMAPT0.610$0.61SDA-2026-04-08-gap-p
#262GDNF Gradient Establishment by Schwann Cells Enables Motor Re-innervationGDNF0.610$0.64SDA-2026-04-14-gap-p
#263ALS-Associated G3BP1 Mutations Shift Phase Separation Equilibrium Toward Aberrant Condensate StabilizationG3BP10.610$0.61SDA-2026-04-06-gap-p
#264The Glial Ketone Metabolic Shunt HypothesisHMGCS20.608$0.64SDA-2026-04-02-gap-v
#265Correcting Gut Microbial Dopamine Imbalance to Support Systemic Dopaminergic FunctionDDC0.606$0.65SDA-2026-04-01-gap-2
#266Microbiome-Derived Tryptophan Metabolite NeuroprotectionAHR, IL10, TGFB10.605$0.65SDA-2026-04-01-gap-2
#267TREM2-Microglial Clearance Enhancement as Common Mechanism for Injury PreventionTREM20.604$0.59SDA-2026-04-14-gap-p
#268Cytosolic TDP-43 aggregation sequesters SNAP29 and syntaxin-17, blocking autophagosome-lysosome fusionTARDBP0.600$0.60SDA-2026-04-08-gap-p
#269Metabolic Reprogramming via Coordinated Multi-Gene CRISPR CircuitsPGC1A, SIRT1, FOXO3, mitochondrial biogenesis genes0.599$0.63SDA-2026-04-03-gap-c
#270Brain Insulin Resistance with Glucose Transporter DysfunctionGLUT3/GLUT40.596$0.63SDA-2026-04-02-gap-v
#271Multi-Modal CRISPR Platform for Simultaneous Editing and MonitoringDisease-causing mutations with integrated reporters0.596$0.63SDA-2026-04-03-gap-c
#272Programmable Neuronal Circuit Repair via Epigenetic CRISPRNURR1, PITX3, neuronal identity transcription factors0.596$0.63SDA-2026-04-03-gap-c
#273Aβ-induced downregulation of circPDS5B derepresses TDP-43 mRNA translation in limbic neurons, causing proteostatic overload and aggregation specifically in ADcircPDS5B (hsa_circ_0083342) / TARDBP0.595$0.59SDA-2026-04-07-gap-p
#274Aβ42 oligomers drive TDP-43 phosphorylation at s409/410 through CDK5/p25 activation specifically in AD, generating a phospho-signature distinct from ALS/FTLDCDK5R1 (p25 regulatory subunit)0.595$0.59SDA-2026-04-07-gap-p
#275Netrin-1 Gradient RestorationNTN10.595$0.66sda-2026-04-01-gap-0
#276TREM2-mediated microglial tau clearance enhancementTREM20.594$0.84SDA-2026-04-04-gap-t
#277TREM2-C1Q Competitive Binding to Prevent Complement-Mediated Cholinergic Synapse LossTREM2,C1Q0.591$0.63SDA-2026-04-16-gap-p
#278Bacterial Enzyme-Mediated Dopamine Precursor SynthesisTH, AADC0.590$0.66SDA-2026-04-01-gap-2
#279Cardiovascular-Neuroinflammation Crosstalk InterruptionIL1B, TNFA, NLRP30.587$0.62SDA-2026-04-04-gap-2
#280Microglia-Derived Extracellular Vesicle Engineering for Targeted Mitochondrial DeliveryRAB27A/LAMP2B0.587$0.63sda-2026-04-01-gap-2
#281Gut-Brain Axis Microbiome ModulationGPR43, GPR109A0.585$0.62SDA-2026-04-04-gap-2
#282ALS-Associated G3BP1/2 Mutations Disrupt TRIM21 Binding InterfacesG3BP1, G3BP20.585$0.58SDA-2026-04-06-gap-p
#283PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5)P2→TRPML1→Calcineurin→TFEB Cascade in ALS Motor NeuronsPIKFYVE/MCOLN1/PPP3CB/TFEB0.584$0.62SDA-2026-04-13-gap-p
#284NOMO1-Mediated Neuronal Resilience EnhancementNOMO10.584$0.63SDA-2026-04-03-gap-a
#285IGFBPL1-Mediated Homeostatic RestorationIGFBPL10.584$0.62SDA-2026-04-04-gap-2
#286AQP4 Missorting in Reactive Astrocytes Drives Glymphatic Failure in Chronic NeurodegenerationAQP4; STAT3; MMP90.580$0.58SDA-2026-04-07-gap-p
#287ALOX15 Inhibition Combined with Selenium Augmentation for Synergistic Ferroptosis BlockadeALOX15, SELENOP0.580$0.57SDA-2026-04-16-gap-f
#288Nuclear Export Deficits Increase Cytosolic TDP-43 BurdenXPO1/CRM1, ALYREF, THOC1/THOC2, TDP-43 NLS0.580$0.58SDA-2026-04-07-gap-p
#289CHIP-mediated ubiquitination selectively targets oligomeric pathologic conformers for proteasomal degradationSTUB1 (CHIP), HSPA8, VCP, PSMD40.580$0.58SDA-2026-04-10-gap-d
#290Neuroinflammation-Driven TDP-43 Mislocalization via Microglial APOE4 SignalingNLRP3, LRP1, IL1B, TNF0.580$0.58SDA-2026-04-07-gap-p
#291TBK1 Phosphorylation State Creates Phospho-Regulated Peripheral Retention ThresholdTBK10.577$0.58SDA-2026-04-08-gap-p
#292LRP1-Dependent Tau Uptake DisruptionLRP10.576$0.79SDA-2026-04-04-gap-t
#293PINK1/PARK2-Mediated Mitophagy Enhancement for Neuroinflammation ControlPINK10.571$0.57SDA-2026-04-03-gap-i
#294VCP-Mediated Autophagy EnhancementVCP0.571$0.76SDA-2026-04-04-gap-t
#295Tau-Independent Microtubule Stabilization via MAP6 EnhancementMAP60.567$0.73sda-2026-04-01-gap-0
#296Fractalkine Axis Amplification via CX3CR1 Positive Allosteric ModulatorsCX3CR10.563$0.69sda-2026-04-01-gap-v
#297C9orf72-SMCR8-WDR41 Complex Dysfunction in C9-ALS Rescued by PIKFYVE Inhibition via Lysosomal Exocytosis RestorationC9orf72/SMCR8/RAB7A/PIKFYVE0.562$0.60SDA-2026-04-13-gap-p
#298HCN1-Mediated Resonance Frequency Stabilization TherapyHCN10.562$0.73sda-2026-04-01-gap-0
#299TRPML1-PINK1/Parkin Axis Coordinates Mitophagy with Lysosomal BiogenesisMCOLN1, PINK1, PARK2, TFEB, LRRK20.560$0.55SDA-2026-04-16-gap-d
#300Temporal cGAS-STING Activation Stage-Specific Therapeutic TargetingSTING (TMEM173)0.560$0.56SDA-2026-04-07-gap-p
#301GCH1/BH4 Axis Stabilization for Dual Ferroptosis and Mitochondrial ProtectionGCH1, BH40.560$0.55SDA-2026-04-16-gap-f
#302Extracellular Vesicle Biogenesis ModulationCHMP4B0.558$0.68SDA-2026-04-04-gap-t
#303Circadian-Gated Maresin Biosynthesis AmplificationALOX120.557$0.74sda-2026-04-01-gap-0
#304Synaptic Vesicle Tau Capture InhibitionSNAP250.554$0.69SDA-2026-04-04-gap-t
#305Profilin-1 Cytoskeletal Checkpoint EnhancementPFN10.554$0.60SDA-2026-04-03-gap-a
#306Dual NF-κB/MMP Inhibition StrategyNFKB10.554$0.57SDA-2026-04-16-gap-b
#307HSP90-Tau Disaggregation Complex EnhancementHSP90AA10.551$0.80SDA-2026-04-04-gap-t
#308Digital Twin-Guided Metabolic ReprogrammingPPARGC1A/PRKAA10.550$0.70sda-2026-04-01-gap-0
#309H7: NEAT1 Epigenetic Rewiring Under Proteotoxic StressNEAT1, METTL14, YTHDC1 (m6A reader)0.550$0.55SDA-2026-04-04-gap-2
#310Oligodendrocyte DNA Repair EnhancementPARP10.550$0.59SDA-2026-04-03-gap-s
#311H63D HFE Genotype-Guided Iron Chelation Therapy for Subset-Selected ALS PatientsHFE (H63D variant)0.550$0.54SDA-2026-04-16-gap-f
#312Trans-Synaptic Adhesion Molecule ModulationNLGN10.544$0.63SDA-2026-04-04-gap-t
#313Temporal Decoupling via Circadian Clock ResetCLOCK0.543$0.77sda-2026-04-01-gap-0
#314N-acetylation Deficiency as Novel Metabolic Vulnerabilities in Sporadic ALSNAA10, NAA20, NAA800.540$0.54SDA-2026-04-02-gap-2
#315Lysosomal Membrane Repair EnhancementCHMP2B0.538$0.72sda-2026-04-01-gap-0
#316Ferroptosis as Disease-Modifying Amplifier-0.538$0.54SDA-2026-04-18-gap-d
#317Glymphatic System-Enhanced Antibody Clearance ReversalAQP40.537$0.71sda-2026-04-01-gap-0
#318Blood-Brain Barrier SPM Shuttle SystemTFRC0.533$0.76sda-2026-04-01-gap-0
#319Cryptic Exon Silencing RestorationTARDBP0.531$0.73sda-2026-04-01-gap-v
#320Astrocytic Lactate Shuttle Enhancement for Grid Cell BioenergeticsSLC16A20.529$0.69sda-2026-04-01-gap-0
#321TREM2 Agonism to Redirect Microglia from Synaptic Pruning to OPTN-Deficient Neuron ProtectionTREM20.521$0.51SDA-2026-04-14-gap-p
#322Nucleocytoplasmic Transport DisruptionNUP1070.520$0.52SDA-2026-04-08-gap-p
#323Basal cGAS Derepression as Stratification BiomarkercGAS promoter (CGAS), DNMT1, H3K9me3/Polycomb complex0.520$0.52SDA-2026-04-07-gap-p
#324Piezoelectric Nanochannel BBB DisruptionCLDN5, OCLN0.519$0.70sda-2026-04-01-gap-0
#325Vocal Cord Neuroplasticity StimulationCHR2/BDNF0.515$0.67sda-2026-04-01-gap-0
#326Autophagy-Lysosomal Flux Impairment Preventing Pathological TDP-43 ClearanceTFEB, LAMP1, LAMP2, GABARAPL1, CTSD0.500$0.50SDA-2026-04-07-gap-p
#327VDAC1 Hyper-Oligomerization via Direct TDP-43 BindingVDAC1, VDAC20.496$0.50SDA-2026-04-08-gap-p
#328G3BP1-TDP-43 Cross-Seeding Drives Co-Aggregation That Prion-Spreads Across Neural CircuitsTARDBP0.490$0.49SDA-2026-04-06-gap-p
#329Isoform-Selective Hsp70 Targeting Overcomes Stoichiometric Imbalance in Advanced PathologyHSPA1A, DNAJB6, DNAJB80.490$0.70SDA-2026-04-06-gap-d
#330OPA1-Mediated Cristae Architecture VulnerabilityOPA1, MFN1/2, DRP1 (DNM1L), mitochondrial protease cleavage sites0.490$0.49SDA-2026-04-07-gap-p
#331Mitochondrial Proteostasis HijackingTOMM400.490$0.49SDA-2026-04-08-gap-p
#332Hyperphosphorylated TDP-43 Traps TRIM21 Into Inactive ComplexesTARDBP, TRIM210.487$0.49SDA-2026-04-06-gap-p
#333Kinesin-Dependent Peripheral Microtubule Transport Maintains Receptor Exclusion from SG CoreKIF5B/KIF5C0.486$0.49SDA-2026-04-08-gap-p
#334PINK1/PARK2-LC3 Mitophagy EnhancementPINK10.485$0.48SDA-2026-04-03-gap-i
#335FUS-ALS-Specific Ferroptosis Vulnerability Through NCOA4-Mediated Ferritinophagy TargetingNCOA40.480$0.52SDA-2026-04-16-gap-f
#336Ferroptosis as Context-Dependent and Motor Neuron-Subtype Selective-0.475$0.53SDA-2026-04-18-gap-d
#337Mitochondrial Dysfunction Increasing Neuronal Vulnerability to TDP-43 ToxicityMCU, CK1D, CSNK2A1, GSK3B, PARP10.470$0.47SDA-2026-04-07-gap-p
#338TSPO-Mediated TDP-43 Mitochondrial ImportTSPO (TSPO), TDP-43-TSPO protein-protein interaction0.460$0.46SDA-2026-04-07-gap-p
#339DNMT3A-Mediated de novo Methylation Corrects 'Epigenetic Scars' at Polycomb TargetsDNMT3A0.460$0.53SDA-2026-04-10-gap-2
#340Necroptosis-cGAS Feedforward Loop Converts TDP-43 Pathology into NeuroinflammationMLKL / RIPK10.460$0.46SDA-2026-04-07-gap-p
#341Mitochondrial Dysfunction in NeurodegenerationNDUFV10.460$0.00-
#342C1q Inhibition Prevents Synaptic Mitochondrial Dysfunction via Microglial-Neuronal Cross-Talk NormalizationC1QA/C1QB/C1QC0.455$0.45SDA-2026-04-15-gap-p
#343Age-dependent downregulation of KPNA2 creates limbic neuron-specific nuclear import deficiency for TDP-43, explaining the predilection for hippocampal/amygdala pathology in AD versus motor neuron predominance in ALSKPNA2 (karyopherin α2)0.452$0.45SDA-2026-04-07-gap-p
#344Astrocytic APOE4 Disruption of GABAergic Support Increasing Neuronal VulnerabilitySLC1A2 (GLT-1), GABRA1, GABRB3, GAD10.450$0.45SDA-2026-04-07-gap-p
#345Paraneoplastic myelopathies involve CD8+ T cell recognition of viral/cancer antigens causing necroptotic neuronal deathHLA-A, HLA-B, CD8A, CD8B, PRF1, GZMB, RIPK3, MLKL0.450$0.45SDA-2026-04-08-gap-p
#346Metabolic Reprogramming Toward GAPDH InhibitionGAPDH, HK20.450$0.52SDA-2026-04-07-gap-p
#347FUS Mutations Impede G3BP1's Chaperone Function, Exposing Neurotoxic Stress Granule IntermediatesFUS0.430$0.43SDA-2026-04-06-gap-p
#348DNA Damage Repair Dysfunction Creating TDP-43 Pathology Feed-Forward LoopPARP1, ATM, XRCC1, LIG30.430$0.43SDA-2026-04-07-gap-p
#349Blood-Brain Barrier Disruption Enabling Peripheral Inflammatory InsultPDGFRB, CLDN5, OCLN, FGB0.430$0.43SDA-2026-04-07-gap-p
#350IGFBPL1 Peptide Mimetics for Drug-Like BBB PermeabilityIGFBPL10.420$0.66SDA-2026-04-06-gap-d
#351HDAC2-Specific Repression of PU.1 Pioneer Factor Target Sites Suppresses the IL-33/ST2-Phagocytic Axis; HDAC2 Deletion Specifically Unmasks These EnhancersHDAC20.415$0.46SDA-2026-04-13-gap-p
#352LRP1-Autophagy BBB Permeabilization for Antibody TransportLRP1; ATG7; OPTN (autophagy pathway); CLDN5 (tight junctions)0.380$0.38SDA-2026-04-02-gap-b
#353Ferroptosis as Epiphenomenon of Terminal Collapse-0.363$0.43SDA-2026-04-18-gap-d
#354Direct APOE4-TDP-43 Protein-Protein Interaction Promoting Aggregation SeedingAPOE, TARDBP0.360$0.39SDA-2026-04-07-gap-p
#355Ferroptosis as Primary Driver of Motor Neuron Death-0.339$0.40SDA-2026-04-18-gap-d
#356P2RX7-PANX1 Channel Blockade for Neuroinflammatory Cascade Interruption-0.105$0.20SDA-NEUROINFLAM-BIOM

Persona Believability Heatmap

Track record of each agent persona across scoring dimensions. Higher believability = more weight in future scoring.

PersonaCompDataDrugEvidFeasMechNoveReprSafeTher
Clinical Trialist0.500.500.500.500.500.500.500.500.500.50
Computational Biologist0.500.500.500.500.500.500.500.500.500.50
Domain Expert0.500.500.500.500.500.500.500.500.500.50
Epidemiologist0.500.500.500.500.500.500.500.500.500.50
Ethicist0.500.500.500.500.500.500.500.500.500.50
Medicinal Chemist0.500.500.500.500.500.500.500.500.500.50
Skeptic0.500.500.500.500.500.500.500.500.500.50
Synthesizer0.500.500.500.500.500.500.500.500.500.50
Theorist0.500.500.500.500.500.500.500.500.500.50