A deadly spread: cellular mechanisms of α-synuclein transfer

Cell Death Differ. 2011 Sep;18(9):1425-33. doi: 10.1038/cdd.2011.53. Epub 2011 May 13.


Classically, Parkinson's disease (PD) is linked to dopamine neuron death in the substantia nigra pars compacta. Intracytoplasmic protein inclusions named Lewy bodies, and corresponding Lewy neurites found in neuronal processes, are also key features of the degenerative process in the substantia nigra. The molecular mechanisms by which substantia nigra dopamine neurons die and whether the Lewy pathology is directly involved in the cell death pathway are open questions. More recently, it has become apparent that Lewy pathology gradually involves greater parts of the PD brain and is widespread in late stages. In this review, we first discuss the role of misfolded α-synuclein protein, which is the main constituent of Lewy bodies, in the pathogenesis of PD. We then describe recent evidence that α-synuclein might transfer between cells in PD brains. We discuss in detail the possible molecular mechanisms underlying the proposed propagation and the likely consequences for cells that take up α-synuclein. Finally, we focus on aspects of the pathogenic process that could be targeted with new pharmaceutical therapies or used to develop biomarkers for early PD detection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyotrophic Lateral Sclerosis / etiology
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Cell Death
  • Dopamine / metabolism
  • Humans
  • Huntington Disease / etiology
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Lewy Bodies / metabolism
  • Lewy Bodies / pathology
  • Mutation
  • Neurites / metabolism
  • Neurites / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Parkinson Disease* / etiology
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / pathology
  • Protein Folding
  • Protein Transport
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*


  • alpha-Synuclein
  • Dopamine