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

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

doi:10.1016/j.neuron.2005.05.010

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

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

410 Scopus citations

Abstract

Abnormal folding of α-synuclein (α-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)α-syn might have therapeutic effects in LBD. For this purpose, hα-syn transgenic (tg) mice were vaccinated with hα-syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated hα-syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal hα-syn associated with the neuronal membrane and promoted the degradation of hα-syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged hα-syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of hα-syn aggregates and that further development of this approach might have a potential role in the treatment of LBD.

Original language	English (US)
Pages (from-to)	857-868
Number of pages	12
Journal	Neuron
Volume	46
Issue number	6
DOIs	https://doi.org/10.1016/j.neuron.2005.05.010
State	Published - Jun 16 2005

Bibliographical note

Funding Information:
This work was supported by NIH grants AG18440, AG5131, and AG022074 and a grant from Elan Pharmaceuticals. The authors wish to thank Jiping Huang and Robin Barbour (Elan Pharmaceuticals) for preparation of the anti-hα-synuclein 9E4 antibody.

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Effects of α-synuclein immunization in a mouse model of Parkinson's disease. / Masliah, Eliezer; Rockenstein, Edward; Adame, Anthony; Alford, Michael; Crews, Leslie; Hashimoto, Makoto; Seubert, Peter; Lee, Michael; Goldstein, Jason; Chilcote, Tamie; Games, Dora; Schenk, Dale.

In: Neuron, Vol. 46, No. 6, 16.06.2005, p. 857-868.

Research output: Contribution to journal › Article › peer-review

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title = "Effects of α-synuclein immunization in a mouse model of Parkinson's disease",

abstract = "Abnormal folding of α-synuclein (α-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)α-syn might have therapeutic effects in LBD. For this purpose, hα-syn transgenic (tg) mice were vaccinated with hα-syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated hα-syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal hα-syn associated with the neuronal membrane and promoted the degradation of hα-syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged hα-syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of hα-syn aggregates and that further development of this approach might have a potential role in the treatment of LBD.",

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

note = "Funding Information: This work was supported by NIH grants AG18440, AG5131, and AG022074 and a grant from Elan Pharmaceuticals. The authors wish to thank Jiping Huang and Robin Barbour (Elan Pharmaceuticals) for preparation of the anti-hα-synuclein 9E4 antibody. ",

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AU - Hashimoto, Makoto

AU - Seubert, Peter

AU - Lee, Michael

AU - Goldstein, Jason

AU - Chilcote, Tamie

AU - Games, Dora

AU - Schenk, Dale

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