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Effects of α-Synuclein Immunization in a Mouse Model of Parkinson’s Disease

2005; Cell Press; Volume: 46; Issue: 6 Linguagem: Inglês

10.1016/j.neuron.2005.05.010

1097-4199

Eliezer Masliah, Edward Rockenstein, Anthony Adame, Michael Alford, Leslie Crews, Makoto Hashimoto, Peter Seubert, Michael Lee, Jason Goldstein, Tamie J. Chilcote, Dora Games, Dale Schenk,

Nerve injury and regeneration

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.