Details

Autor(en) / Beteiligte

• Matsuoka, Yasuji
• Vila, Miquel
• Lincoln, Sarah
• McCormack, Alison
• Picciano, Melanie
• Lafrancois, John
• Yu, Xin
• Dickson, Dennis
• Langston, William J
• McGowan, Eileen
• Farrer, Matt
• Hardy, John
• Duff, Karen
• Przedborski, Serge
• Di Monte, Donato A

Titel

Lack of Nigral Pathology in Transgenic Mice Expressing Human a-Synuclein Driven by the Tyrosine Hydroxylase Promoter

Ist Teil von

• Neurobiology of disease, 2001-06, Vol.8 (3), p.535-539

Erscheinungsjahr

2001

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• a-Synuclein has been identified as a major component of Lewy body inclusions, which are one of the pathologic hallmarks of idiopathic Parkinson's disease. Mutations in a-synuclein have been found to be responsible for rare familial cases of Parkinsonism. To test whether overexpression of human a-synuclein leads to inclusion formation and neuronal loss of dopaminergic cells in the substantia nigra, we made transgenic mice in which the expression of wild-type or mutant (A30P and A53T) human a-synuclein protein was driven by the promoter from the tyrosine hydroxylase gene. Even though high levels of human a-synuclein accumulated in dopaminergic cell bodies, Lewy-type-positive inclusions did not develop in the nigrostriatal system. In addition, the number of nigral neurons and the levels of striatal dopamine were unchanged relative to non-transgenic littermates, in mice up to one year of age. These findings suggest that overexpression of a-synuclein within nigrostriatal dopaminergic neurons is not in itself sufficient to cause aggregation into Lewy body-like inclusions, nor does it trigger overt neurodegenerative changes.