🧪
hypothesis

ER-mitochondria contact-site dysfunction in neurodegeneration

Hypothesis

ER-mitochondria contact-site dysfunction in neurodegeneration

Altered mitochondria-associated membranes may disrupt calcium transfer, lipid synthesis, ROS handling, and apoptotic thresholds in neurodegeneration.
🧬 MFN2; ITPR1; HSPA9; VDAC1🩺 neurodegeneration🎯 Composite 53%💱 $0.52▼1.3%proposed
EvidencePending (0%)📖 0 cit🗣 1 debates 3 support 2 oppose
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Composite53%

🧪 Overview

Altered mitochondria-associated membranes may disrupt calcium transfer, lipid synthesis, ROS handling, and apoptotic thresholds in neurodegeneration. The hypothesis needs disease-, cell-type-, and stage-specific directionality because either excessive coupling, insufficient coupling, or altered contact composition could be pathogenic.

🧬 Mechanism

No curated mechanism pathway recorded for this hypothesis.

⚖️ Evidence

⚖️ Evidence Matrix3 supports2 contradicts
Supports
MFN2 mutations cause Charcot-Marie-Tooth disease type 2A, linking ER-mitochondria and mitochondrial dynamics machinery to neurodegeneration.
PMID:15194654
Supports
MAM dysfunction has been reported in AD models.
PMID:28973123
Supports
Presenilins regulate ER-mitochondria coupling, connecting familial AD biology to MAM function.
PMID:20133786
Contradicts
MAM dysfunction is directionally ambiguous; too much, too little, or altered composition may each occur depending on model and disease stage.
PMID:28973123
Contradicts
Proximity assays can show organelle closeness without proving functional calcium transfer, lipid flux, respiration, survival benefit, or therapeutic direction.
PMID:unassigned
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — MFN2;

No curated PDB or AlphaFold mapping for MFN2; yet. Search RCSB →

💉 Clinical Trials

No clinical trials data linked to this hypothesis yet.

No curated ClinVar variants loaded for this hypothesis.

Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.

🔍 Search ClinVar for MFN2; ITPR1; HSPA9; VDAC1 →

No DepMap CRISPR Chronos data found for MFN2; ITPR1; HSPA9; VDAC1.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

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