Innate Immune Discrimination Failure In α-Synuclein Pathology: A Mimicry Framework

Overview

Neurodegenerative diseases such as Parkinson's are predominantly framed as problems of protein accumulation and downstream clearance, implicitly assuming that pathogenic conformations are sufficiently distinguishable for targeted intervention. Yet current therapies remain largely symptomatic, lacking capacity to directly engage the underlying protein pathology.  I propose a mechanistic framework in which proteinopathies arise from failures of innate immune discrimination at the structural level. Through computational analysis of α-synuclein conformations, I evaluated surface accessibility and hydrophobic patterning to assess whether aggregated species present unique signatures for selective recognition. The results reveal substantial feature overlap, suggesting that misfolded proteins may evade detection rather than solely resist clearance. I therefore introduce a mimicry-based strategy that inverts molecular mimicry, typically a driver of pathological misrecognition to a tool for selective targeting, reframing intervention as a problem of discrimination, not solely delivery.

Awards (2)

• Bronze Medal
• Selected for CWSF 2026

Competition history

• CWSF 2026 Disease & Illness

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