How strong is the evidence that Parkinson's disease is a prion disorder?

Patrik Brundin, Jiyan Ma, Jeffrey H. Kordower

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations

Abstract

Purpose of review We describe evidence supporting the hypothesis that α-synuclein has a prion-like role in Parkinson's disease and related α-synucleinopathies, and discuss how this novel thinking impacts the development of diagnostics and disease-modifying therapies. Recent findings Observations that immature dopamine neurons grafted to Parkinson's disease patients can develop Lewy bodies triggered a surge of interest in the putative prion-like properties of α-synuclein. We recount results from experiments which confirm that misfolded α-synuclein can exhibit disease-propagating properties, and describe how they relate to the spreading of α-synuclein aggregates in α-synucleinopathies. We share insights into the underlying molecular mechanisms and their relevance to novel therapeutic targets. Finally, we discuss what the initial triggers of α-synuclein misfolding might be, where in the body the misfolding events might take place, and how this can instruct development of novel diagnostic tools. We speculate that differences in anatomical trigger sites and variability in α-synuclein fibril structure can contribute to clinical differences between α-synucleinopathies. Summary The realization that α-synuclein pathology can propagate between brain regions in neurodegenerative diseases has deepened and expanded our understanding of potential pathogenic processes which can lead to the development of novel diagnostic tools as well as the identification of new therapeutic targets.

Original languageEnglish (US)
Pages (from-to)459-466
Number of pages8
JournalCurrent Opinion in Neurology
Volume29
Issue number4
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Keywords

  • Lewy body
  • Parkinson's disease
  • prion-like
  • α-synuclein

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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