Review/Commentary

Can infections trigger alpha-synucleinopathies? - PMC

/PMC/2026

Why It Matters

If you're tracking Parkinson's risk factors, this matters because infections aren't just acute problems — they might set off a decades-long cascade of protein misfolding. The gut connection is particularly interesting: gastrointestinal infections years before motor symptoms appear could be an early warning sign. This reframes infection prevention as potentially relevant to neurodegenerative disease risk, not just immediate illness.

Key Findings

  • Multiple pathogens (H. pylori, influenza, herpes viruses, fungi, and parasites) show associations with increased Parkinson's disease risk in epidemiological studies, though causation isn't proven
  • Alpha-synuclein appears to function as an antimicrobial peptide, suggesting its aggregation might be a maladaptive immune response rather than purely pathological
  • Gastrointestinal infections are particularly relevant — constipation and GI dysfunction often precede Parkinson's motor symptoms by years, consistent with the Braak hypothesis of gut-to-brain disease progression
  • Pathogens can trigger alpha-synuclein misfolding through multiple mechanisms: direct binding to the protein, chronic neuroinflammation, disruption of autophagy, and molecular mimicry
  • The blood-brain barrier becomes more permeable during systemic infections, potentially allowing misfolded proteins or inflammatory signals to reach the brain