| Literature DB >> 12034752 |
Philipp J Kahle1, Manuela Neumann, Laurence Ozmen, Veronika Muller, Helmut Jacobsen, Will Spooren, Babette Fuss, Barbara Mallon, Wendy B Macklin, Hideo Fujiwara, Masato Hasegawa, Takeshi Iwatsubo, Hans A Kretzschmar, Christian Haass.
Abstract
(Oligodendro)glial cytoplasmic inclusions composed of alpha-synuclein (alpha SYN) characterize multiple system atrophy (MSA). Mature oligodendrocytes (OLs) do not normally express alpha SYN, so MSA pathology may arise from aberrant expression of alpha SYN in OLs. To study pathological deposition of alpha SYN in OLs, transgenic mice were generated in which human wild-type alpha SYN was driven by a proteolipid protein promoter. Transgenic alpha SYN was detected in OLs but no other brain cell type. At the light microscopic level, the transgenic alpha SYN profiles resembled glial cytoplasmic inclusions. Strikingly, the diagnostic hyperphosphorylation at S129 of alpha SYN was reproduced in the transgenic mice. A significant proportion of the transgenic alpha SYN was detergent insoluble, as in MSA patients. The histological and biochemical abnormalities were specific for the disease-relevant alpha SYN because control green fluorescent protein was fully soluble and evenly distributed throughout OL cell bodies and processes. Thus, ectopic expression alpha SYN in OLs might initiate salient features of MSA pathology.Entities:
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Year: 2002 PMID： 12034752 PMCID： PMC1084143 DOI： 10.1093/embo-reports/kvf109
Source DB: PubMed Journal: EMBO Rep ISSN： 1469-221X Impact factor: 8.807