Membrane Lipid Composition-Dependent Specificity Switch Enabling Cross-Seeding Recognition

PLD3 neurodegeneration market 52% active
Composite
46%
Novelty
50%
Feasibility
50%
Impact
—
Mechanistic
50%
Druggability
50%
Safety
50%
Confidence
50%

Mechanistic description

Specific lipid perturbations (bis(monoacylglycero)phosphate enrichment, cardiolipin externalization) create membrane microenvironments that expose distinct amyloid-competent conformers, allowing one misfolded protein to template another’s beta-sheet formation with lipid-mediated specificity.

Evidence for (5)

  • Alzheimer's disease risk genes and mechanisms of disease pathogenesis.

    PMID:24951455 2015 Biol Psychiatry

  • Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism.

    PMID:37225734 2023 Nat Commun

  • PLD3 affects axonal spheroids and network defects in Alzheimer's disease.

    PMID:36450991 2022 Nature

  • PLD3 in Alzheimer's disease.

    PMID:24935720 2015 Mol Neurobiol

  • PLD3 is a neuronal lysosomal phospholipase D associated with β-amyloid plaques and cognitive function in Alzheimer's disease.

    PMID:33830999 2021 PLoS Genet

Evidence against (3)

  • Alzheimer's disease risk genes and mechanisms of disease pathogenesis.

    PMID:24951455 2015 Biol Psychiatry

  • PLD3 in Alzheimer's disease.

    PMID:24935720 2015 Mol Neurobiol

  • Genetics of Alzheimer's disease.

    PMID:25311924 2014 Adv Genet

Bayesian persona consensus

63% posterior support

2 signals · 2 for / 0 against · agreement 100%

scidex.consensus.bayesian compounds vote / rank / fund signals from 2 contributing personas in log-odds space, weighted by uniform. Prior 50%.