SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease.
The pre-synaptic protein alpha-synuclein is the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies. Mutations in the alpha-synuclein gene cause familial forms of Parkinson's disease and dement...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2010
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| _version_ | 1797079415380770816 |
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| author | Garcia-Reitböck, P Anichtchik, O Bellucci, A Iovino, M Ballini, C Fineberg, E Ghetti, B Della Corte, L Spano, P Tofaris, G Goedert, M Spillantini, MG |
| author_facet | Garcia-Reitböck, P Anichtchik, O Bellucci, A Iovino, M Ballini, C Fineberg, E Ghetti, B Della Corte, L Spano, P Tofaris, G Goedert, M Spillantini, MG |
| author_sort | Garcia-Reitböck, P |
| collection | OXFORD |
| description | The pre-synaptic protein alpha-synuclein is the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies. Mutations in the alpha-synuclein gene cause familial forms of Parkinson's disease and dementia with Lewy bodies. We previously described a transgenic mouse line expressing truncated human alpha-synuclein(1-120) that develops alpha-synuclein aggregates, striatal dopamine deficiency and reduced locomotion, similar to Parkinson's disease. We now show that in the striatum of these mice, as in Parkinson's disease, synaptic accumulation of alpha-synuclein is accompanied by an age-dependent redistribution of the synaptic SNARE proteins SNAP-25, syntaxin-1 and synaptobrevin-2, as well as by an age-dependent reduction in dopamine release. Furthermore, the release of FM1-43 dye from PC12 cells expressing either human full-length alpha-synuclein(1-140) or truncated alpha-synuclein(1-120) was reduced. These findings reveal a novel gain of toxic function of alpha-synuclein at the synapse, which may be an early event in the pathogenesis of Parkinson's disease. |
| first_indexed | 2024-03-07T00:45:30Z |
| format | Journal article |
| id | oxford-uuid:847f9cef-21db-4296-b8b1-6a2cb0eab94b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:45:30Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:847f9cef-21db-4296-b8b1-6a2cb0eab94b2022-03-26T21:51:30ZSNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:847f9cef-21db-4296-b8b1-6a2cb0eab94bEnglishSymplectic Elements at Oxford2010Garcia-Reitböck, PAnichtchik, OBellucci, AIovino, MBallini, CFineberg, EGhetti, BDella Corte, LSpano, PTofaris, GGoedert, MSpillantini, MGThe pre-synaptic protein alpha-synuclein is the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies. Mutations in the alpha-synuclein gene cause familial forms of Parkinson's disease and dementia with Lewy bodies. We previously described a transgenic mouse line expressing truncated human alpha-synuclein(1-120) that develops alpha-synuclein aggregates, striatal dopamine deficiency and reduced locomotion, similar to Parkinson's disease. We now show that in the striatum of these mice, as in Parkinson's disease, synaptic accumulation of alpha-synuclein is accompanied by an age-dependent redistribution of the synaptic SNARE proteins SNAP-25, syntaxin-1 and synaptobrevin-2, as well as by an age-dependent reduction in dopamine release. Furthermore, the release of FM1-43 dye from PC12 cells expressing either human full-length alpha-synuclein(1-140) or truncated alpha-synuclein(1-120) was reduced. These findings reveal a novel gain of toxic function of alpha-synuclein at the synapse, which may be an early event in the pathogenesis of Parkinson's disease. |
| spellingShingle | Garcia-Reitböck, P Anichtchik, O Bellucci, A Iovino, M Ballini, C Fineberg, E Ghetti, B Della Corte, L Spano, P Tofaris, G Goedert, M Spillantini, MG SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. |
| title | SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. |
| title_full | SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. |
| title_fullStr | SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. |
| title_full_unstemmed | SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. |
| title_short | SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. |
| title_sort | snare protein redistribution and synaptic failure in a transgenic mouse model of parkinson s disease |
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