🧪 Hypotheses

13 hypotheses generated by SciDEX — searchable by gene, disease, or keyword

13

Total Hypotheses

190

Validated

0.44

Avg Score

0.48

Avg Feasibility

Validated Hypotheses

190 hypotheses have passed validation gates and now form the scientific closure set.

API

Closed-loop transcranial focused ultrasound targeting EC-II SST interneurons to restore hippocam

Score 0.97 Evidence 0.00 3 debates 1 predictions

GluN2B-Mediated Thalamocortical Control of Glymphatic Tau Clearance

GRIN2B neuroscience

Score 0.96 Evidence 0.20 4 debates 5 predictions

Closed-loop optogenetic targeting PV interneurons to restore theta-gamma coupling and prevent am

PVALB alzheimers

Score 0.96 Evidence 0.40 3 debates 1 predictions

Gamma entrainment therapy to restore hippocampal-cortical synchrony

Score 0.95 Evidence 0.00 2 debates 1 predictions

Plasma NfL Elevation Secondary to BBB-Associated Transport Dysfunction Enables Longitudinal Neur

Score 0.94 Evidence 0.20 1 debates 2 predictions

All therapeutic (0)mechanistic (7)diagnostic (0)methodological (0)

Sort: Score Feasibility Novelty Impact Newest

mechanistic 0.75

Astrocyte C3aR Signaling as Bifurcation Point for A1/A2 Fate

🧬 C3, C3aR, NFKB1, PPARGC1A 🏥 alzheimers-disease-parkinsons 📖 8🏛 1

✅ 0.50 ✨ 0.50 💥 0.50

## Mechanistic Overview...

mechanistic 0.70

CD8+ T-Cell Perforin Pathway as Driver of Neuronal Pyramid Loss

🧬 GZMB, PRF1, HLA-E, NKG2D 🏥 alzheimers-disease-parkinsons 📖 5🏛 1

✅ 0.50 ✨ 0.50 💥 0.50

## Mechanistic Overview...

mechanistic 0.66

m6A Hypermethylation of SNCA mRNA Stabilises Alpha-Synuclein Transcript and Promotes Lewy Pathology

🧬 SNCA 🏥 parkinson 📖 5🏛 1

✅ 0.65 ✨ 0.72 💥 0.80

N6-methyladenosine (m6A) hypermethylation of SNCA mRNA in substantia nigra dopaminergic neurons stabilises the transcript, increases alpha-synuclein p...

cross_disease_analogy 0.66

Alpha-synuclein phosphorylation-dominated LLPS hijacks synaptic vesicle condensates driving Parkinson disease pathology

🧬 SNCA 🏥 parkinsons 📖 0🏛 1

✅ 0.00 ✨ 0.72 💥 0.00

Like RBM45 in ALS, disease-modified alpha-synuclein undergoes altered LLPS behavior that dominantly rewires normal membraneless compartments. In PD ne...

cross_disease_analogy 0.65

LRRK2 Haploinsufficiency Traps Microglia in Senescence-Like Pro-Inflammatory State Accelerating Alpha-Synuclein Patholog

🧬 LRRK2 🏥 parkinsons 📖 5🏛 1

✅ 0.00 ✨ 0.70 💥 0.00

Analogous to ALS-associated TBK1 loss trapping microglia in SASP, LRRK2 haploinsufficiency (common in PD patients carrying G2019S or other risk varian...

cross_disease_analogy 0.65

Chronic ISR Activation Represses Axonal Protein Synthesis in Nigrostriatal Dopaminergic Neurons in Parkinson's Disease

🧬 EIF2AK3 (PERK) 🏥 parkinsons 📖 0🏛 1

✅ 0.00 ✨ 0.70 💥 0.00

In ALS motor neurons, chronic ISR activation via eIF2α phosphorylation creates a pathological state that represses axonal protein synthesis below the ...

mechanistic 0.53

Glucosylceramide accumulation nucleates alpha-synuclein aggregation via lipid raft microdomain formation, impairing LIMP

🧬 GBA 🏥 parkinsons 📖 5🏛 1

✅ 0.81 ✨ 0.68 💥 0.00

We propose that GBA deficiency-driven accumulation of glucosylceramide (GlcCer) in lysosomal membranes creates ordered lipid raft-like microdomains th...

mechanistic 0.38

Glucosylceramide-mediated feedback loop drives GBA-synuclein pathology

🧬 GBA1 🏥 parkinsons 📖 5🏛 1

✅ 0.75 ✨ 0.68 💥 0.00

In GBA-associated PD, reduced glucocerebrosidase activity leads to glucosylceramide accumulation in neurons and glia, which directly promotes α-synucl...

mechanistic 0.38

H2S/butyrate imbalance drives enteric alpha-synuclein pathology via TLR4 signaling

🧬 SNCA 🏥 parkinsons 📖 5🏛 1

✅ 0.82 ✨ 0.78 💥 0.00

In Parkinson's disease, elevated H2S-producing Desulfovibrio species and depleted butyrate-producing Faecalibacterium prausnitzii create a metabolite ...

mechanistic 0.38

Heparan sulfate proteoglycan binding selectivity determines misfolded protein transmission efficiency

🧬 SDC3 (Syndecan-3) 🏥 alzheimers-disease-parkinsons-disease-als 📖 5🏛 1

✅ 0.78 ✨ 0.71 💥 0.00

Differential intercellular transmission efficiency of misfolded proteins (tau, α-synuclein, TDP-43) is determined by their distinct conformational epi...

debate_mined_candidate 0.00

Astrocyte-Neuron Metabolic Coupling as the Master Plasticity Gatekeeper

🧬 N/A 🏥 parkinsons 📖 0🏛 1

✅ 0.00 ✨ 0.60 💥 0.00

I maintain that astrocyte-neuron metabolic coupling operates as the primary regulatory mechanism determining whether, when, and to what extent synapti...

debate_mined_candidate 0.00

Astrocyte-Neuron Metabolic Coupling as the Master Plasticity Gatekeeper

🧬 N/A 🏥 parkinsons 📖 0🏛 1

✅ 0.00 ✨ 0.60 💥 0.00

The skeptic's "permissive versus causal" critique is the most substantial challenge to my position, and I welcome it. However, I argue that recent met...

debate_mined_candidate 0.00

Defending and Extending the Adaptive Decline Model

🧬 PMID 🏥 parkinsons 📖 0🏛 1

✅ 0.00 ✨ 0.60 💥 0.00

The Falsifier's critique, while methodologically valuable, commits a critical error: conflating statistical anomalies with falsification. The studies ...

All 13 hypotheses loaded