Immunotherapy targeting α-synuclein, with relevance for future treatment of Parkinson's disease and other Lewy body disorders

Immunotherapy. 2014;6(2):141-53. doi: 10.2217/imt.13.162.


Immunotherapy targeting α-synuclein has evolved as a potential therapeutic strategy for neurodegenerative diseases, such as Parkinson's disease, and initial studies on cellular and animal models have shown promising results. α-synuclein vaccination of transgenic mice reduced the number of brain inclusions, whereas passive immunization studies demonstrated that antibodies against the C-terminus of α-synuclein can pass the blood-brain barrier and affect the pathology. In addition, preliminary evidence suggests that transgenic mice treated with an antibody directed against α-synuclein oligomers/protofibrils resulted in reduced levels of such species in the CNS. The underlying mechanisms of immunotherapy are not yet fully understood, but may include antibody-mediated clearance of pre-existing aggregates, prevention of protein propagation between cells and microglia-dependent protein clearance. Thus, immunotherapy targeting α-synuclein holds promise, but needs to be further developed as a future disease-modifying treatment in Parkinson's disease and other α-synucleinopathies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Humans
  • Immunotherapy* / trends
  • Lewy Bodies / metabolism*
  • Lewy Body Disease / immunology
  • Lewy Body Disease / therapy*
  • Mice
  • Mice, Transgenic
  • Molecular Targeted Therapy
  • Parkinson Disease / immunology
  • Parkinson Disease / therapy*
  • Unfolded Protein Response / immunology
  • alpha-Synuclein / genetics
  • alpha-Synuclein / immunology*


  • Antibodies, Monoclonal
  • alpha-Synuclein