Immunotherapy in Parkinson's Disease: Micromanaging Alpha-Synuclein Aggregation

J Parkinsons Dis. 2015;5(3):413-24. doi: 10.3233/JPD-150630.


Currently, several α-synuclein immunotherapies are being tested in experimental Parkinson's disease models and in clinical trials. Recent research has revealed that α-synuclein is not just an intracellular synaptic protein but also exists extracellularly. Moreover, the transfer of misfolded α-synuclein between cells might be a crucial step in the process leading to a progressive increase in deposition of α-synuclein aggregates throughout the Parkinson's disease brain. The revelation that α-synuclein is present outside cells has increased the interest in antibody-based therapies and opens up for the notion that microglia might play a key role in retarding Parkinson's disease progression. The objectives of this review are to describe and contrast the use of active and passive immunotherapy in treating α-synucleinopathies and highlight the likely important role of microglia in clearing misfolded α-synuclein from the extracellular space.

Keywords: Parkinson’s disease; alpha synuclein; immunotherapy; microglia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies
  • Blood-Brain Barrier / immunology
  • Brain / immunology
  • Brain / metabolism
  • Clinical Trials as Topic
  • Encephalitis / immunology
  • Encephalitis / metabolism
  • Humans
  • Immunotherapy*
  • Microglia / immunology
  • Microglia / metabolism
  • Neurons / immunology
  • Neurons / metabolism
  • Parkinson Disease / immunology
  • Parkinson Disease / metabolism
  • Parkinson Disease / therapy*
  • Protein Aggregation, Pathological*
  • alpha-Synuclein / metabolism*


  • Antibodies
  • alpha-Synuclein