Effects of alpha-synuclein immunization in a mouse model of Parkinson's disease

Neuron. 2005 Jun 16;46(6):857-68. doi: 10.1016/j.neuron.2005.05.010.


Abnormal folding of alpha-synuclein (alpha-syn) is thought to lead to neurodegeneration and the characteristic symptoms of Lewy body disease (LBD). Since previous studies suggest that immunization might be a potential therapy for Alzheimer's disease, we hypothesized that immunization with human (h)alpha-syn might have therapeutic effects in LBD. For this purpose, halpha-syn transgenic (tg) mice were vaccinated with halpha-syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated halpha-syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal halpha-syn associated with the neuronal membrane and promoted the degradation of halpha-syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged halpha-syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of halpha-syn aggregates and that further development of this approach might have a potential role in the treatment of LBD.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Antibodies / therapeutic use
  • Blotting, Western / methods
  • Cathepsin D / metabolism
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Diagnostic Imaging / methods
  • Disease Models, Animal*
  • Epitope Mapping / methods
  • Humans
  • Immunization / methods*
  • Immunohistochemistry / methods
  • Inclusion Bodies / metabolism
  • Lysosomes / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Immunological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology*
  • Neuroglia / metabolism
  • Neurons / metabolism
  • Parkinson Disease / immunology*
  • Parkinson Disease / metabolism
  • Parkinson Disease / therapy*
  • Presynaptic Terminals / metabolism
  • Subcellular Fractions / metabolism
  • Synaptophysin / metabolism
  • Synucleins
  • alpha-Synuclein


  • Antibodies
  • Nerve Tissue Proteins
  • SNCA protein, human
  • Snca protein, mouse
  • Synaptophysin
  • Synucleins
  • alpha-Synuclein
  • Cathepsin D