early PD proteogenomic hubs that are both causal enough and accessible enough to perturb as proximal driver in Proteogenomic Network Hubs as Druggable Targets in Early PD Neurodegeneration

SNCA neurodegeneration market 63% proposed
Composite
63%
Novelty
72%
Feasibility
67%
Impact
64%
Mechanistic
70%
Druggability
54%
Safety
52%
Confidence
62%

Mechanistic description

early PD proteogenomic hubs that are both causal enough and accessible enough to perturb should produce a measurable proximal phenotype before late disease pathology. The decisive test is multi-omics network centrality, druggability scoring, interactome validation, and SNCA iPSC-neuron perturbation assays.

Evidence for (6)

  • Review identified convergent pathogenic mechanisms but highlighted that druggability assessment of network hubs in early PD remains an open challenge.

    Key genes and convergent pathogenic mechanisms in Parkinson disease

  • Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disease.

    PMID:33182554 2020 Int J Mol Sci

  • Neurotrophins and neurodegeneration.

    PMID:12787319 2003 Neuropathol Appl Neurobiol

  • LRRK2 and neurodegeneration.

    PMID:19142648 2009 Acta Neuropathol

  • Oligodendrocytes drive neuroinflammation and neurodegeneration in Parkinson's disease via the prosaposin-GPR37-IL-6 axis.

    PMID:39913287 2025 Cell Rep

  • GBA-associated PD. Neurodegeneration, altered membrane metabolism, and lack of energy failure.

    PMID:22722629 2012 Neurology

Evidence against (1)

  • network hubs are often essential, pleiotropic, or inaccessible to safe pharmacologic modulation

    Key genes and convergent pathogenic mechanisms in Parkinson disease

Bayesian persona consensus

55% posterior support

1 signal · 1 for / 0 against · agreement 100%

scidex.consensus.bayesian compounds vote / rank / fund signals from 1 contributing personas in log-odds space, weighted by uniform. Prior 50%.