Infections in the Etiology of Parkinson's Disease and Synucleinopathies: A Renewed Perspective, Mechanistic Insights, and Therapeutic Implications

Gabriela Mercado, Christopher Kaeufer, Franziska Richter, Wouter Peelaerts

Research output: Contribution to journalReview articlepeer-review

Abstract

Increasing evidence suggests a potential role for infectious pathogens in the etiology of synucleinopathies, a group of age-related neurodegenerative disorders including Parkinson's disease (PD), multiple system atrophy and dementia with Lewy bodies. In this review, we discuss the link between infections and synucleinopathies from a historical perspective, present emerging evidence that supports this link, and address current research challenges with a focus on neuroinflammation. Infectious pathogens can elicit a neuroinflammatory response and modulate genetic risk in PD and related synucleinopathies. The mechanisms of how infections might be linked with synucleinopathies as well as the overlap between the immune cellular pathways affected by virulent pathogens and disease-related genetic risk factors are discussed. Here, an important role for α-synuclein in the immune response against infections is emerging. Critical methodological and knowledge gaps are addressed, and we provide new future perspectives on how to address these gaps. Understanding how infections and neuroinflammation influence synucleinopathies will be essential for the development of early diagnostic tools and novel therapies.

Original languageEnglish (US)
Pages (from-to)1301-1329
Number of pages29
JournalJournal of Parkinson's Disease
Volume14
Issue number7
DOIs
StatePublished - Oct 15 2024

Keywords

  • Parkinson's disease
  • infections
  • multiple system atrophy
  • α-synuclein

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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