Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alpha-synuclein(1-120): implications for Lewy body disorders.

Journal article

Dysfunction of the 140 aa protein alpha-synuclein plays a central role in Lewy body disorders, including Parkinson's disease, as well as in multiple system atrophy. Here, we show that the expression of truncated human alpha-synuclein(1-120), driven by the rat tyrosine hydroxylase promoter on a mouse alpha-synuclein null background, leads to the formation of pathological inclusions in the substantia nigra and olfactory bulb and to a reduction in striatal dopamine levels. At the behavioral level, the transgenic mice showed a progressive reduction in spontaneous locomotion and an increased response to amphetamine. These findings suggest that the C-terminal of alpha-synuclein is an important regulator of aggregation in vivo and will help to understand the mechanisms underlying the pathogenesis of Lewy body disorders and multiple system atrophy.

Authors: Tofaris, G; Garcia Reitböck, P; Humby, T; Lambourne, S; O'Connell, M

• Journal: Journal of neuroscience : the official journal of the Society for Neuroscience
• Volume: 26
• Issue: 15
• Pages: 3942-3950
• Publication date: 2006-04-01
• DOI: 10.1523/jneurosci.4965-05.2006
• EISSN: 1529-2401
• ISSN: 0270-6474
• Language: English
• Keywords: Promoter Regions, Genetic; Mice, Inbred CBA; Lewy Body Disease; Mice, Inbred C57BL; Animals; Tyrosine 3-Monooxygenase; Substantia Nigra; Neurons; Rats; Parkinson Disease; Mice; Mice, Transgenic; Humans; alpha-Synuclein; Olfactory Bulb; Lewy Bodies; Dopamine