title: Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders.
abstract: To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.
authors.affiliation: Department of Neurosciences, Department of Pathology, University of California San Diego, La Jolla, CA 92093-0624, USA. emasliah@ucsd.edu
authors.forename: E
authors.initials: E
authors.lastname: Masliah
authors.forename: E
authors.initials: E
authors.lastname: Rockenstein
authors.forename: I
authors.initials: I
authors.lastname: Veinbergs
authors.forename: M
authors.initials: M
authors.lastname: Mallory
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
authors.forename: A
authors.initials: A
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Sagara
authors.forename: A
authors.initials: A
authors.lastname: Sisk
authors.forename: L
authors.initials: L
authors.lastname: Mucke
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000648:ultrastructure; D016631:Lewy Bodies / Q000648:ultrastructure; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D013378:Substantia Nigra / Q000378:metabolism / Q000648:ultrastructure; D051843:Synucleins; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D014452:Ubiquitins; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine