| Literature DB >> 15953415 |
Eliezer Masliah1, Edward Rockenstein, Anthony Adame, Michael Alford, Leslie Crews, Makoto Hashimoto, Peter Seubert, Michael Lee, Jason Goldstein, Tamie Chilcote, Dora Games, Dale Schenk.
Abstract
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.Entities:
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Year: 2005 PMID： 15953415 DOI： 10.1016/j.neuron.2005.05.010
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173