title: 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.
abstract: 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.affiliation: Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 2PY, United Kingdom.
authors.forename: George K
authors.initials: GK
authors.lastname: Tofaris
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia Reitböck
authors.forename: Trevor
authors.initials: T
authors.lastname: Humby
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Lambourne
authors.forename: Mark
authors.initials: M
authors.lastname: O'Connell
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Helen
authors.initials: H
authors.lastname: Gossage
authors.forename: Piers C
authors.initials: PC
authors.lastname: Emson
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Wilkinson
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
mesh_terms: D000818:Animals; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D020961:Lewy Body Disease / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology*; D009830:Olfactory Bulb / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D051381:Rats; D013378:Substantia Nigra / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine