Publication Date:
2000-02-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Masliah, E -- Rockenstein, E -- Veinbergs, I -- Mallory, M -- Hashimoto, M -- Takeda, A -- Sagara, Y -- Sisk, A -- Mucke, L -- AG10689/AG/NIA NIH HHS/ -- AG11385/AG/NIA NIH HHS/ -- AG5131/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2000 Feb 18;287(5456):1265-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosciences, Department of Pathology, University of California San Diego, La Jolla, CA 92093-0624, USA. emasliah@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10678833" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Brain/*metabolism/ultrastructure
;
Dopamine/*physiology
;
Humans
;
Inclusion Bodies/*metabolism/ultrastructure
;
Lewy Bodies/ultrastructure
;
Lewy Body Disease/metabolism/pathology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Inbred DBA
;
Mice, Transgenic
;
Microscopy, Electron
;
Motor Activity
;
Nerve Tissue Proteins/genetics/immunology/*metabolism
;
Neurodegenerative Diseases/*metabolism/pathology
;
Neurons/*metabolism/ultrastructure
;
Substantia Nigra/metabolism/ultrastructure
;
Synucleins
;
Tyrosine 3-Monooxygenase/immunology/metabolism
;
Ubiquitins/metabolism
;
alpha-Synuclein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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