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.
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.
Pubmed ID: 16611810 RIS Download
Animals | Dopamine | Humans | Lewy Bodies | Lewy Body Disease | Mice | Mice, Inbred C57BL | Mice, Inbred CBA | Mice, Transgenic | Neurons | Olfactory Bulb | Parkinson Disease | Promoter Regions, Genetic | Rats | Substantia Nigra | Tyrosine 3-Monooxygenase | alpha-Synuclein