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Formation of parkin aggregates and enhanced PINK1 accumulation during the pathogenesis of Parkinson's disease.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2010 Mar 19; Vol. 393 (4), pp. 824-8. Date of Electronic Publication: 2010 Feb 18. - Publication Year :
- 2010
-
Abstract
- Parkinson's disease (PD) is a devastating neurodegenerative disease characterized by a distinct set of motor symptoms. Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) or parkin have been linked to early-onset autosomal recessive forms of familial PD. We have recently shown that parkin (an E3 ubiquitin ligase) and PINK1 (a serine/threonine kinase) affect one other's stability, solubility, and tendency to form cytoprotective aggresomes (Um et al., 2009). Here we validated the functional relevance of this mutual interaction under pathologic PD conditions, by investigating the changes of expression and solubility of these factors in response to PD-linked toxins. Consistent with our previous cell culture data, exposure of human dopaminergic neuroblastoma SH-SY5Y cells to PD-linked toxins (1-methyl-4-phenylpyridinium ion, 6-hydroxydopamine, or MG132) reduced Nonidet P-40-soluble parkin levels and induced PINK1 accumulation. Consistent with our previous findings from parkin knockout mice, rat models of PD (6-hydroxydopamine-, rotenone-, or MG132-induced PD) were also associated with an increase in soluble and insoluble PINK1 levels as well as enhanced formation of parkin aggregates. These findings suggest that both PINK1 and parkin play important roles in regulating the formation of Lewy bodies during the pathogenesis of sporadic and familial PD.<br /> (Copyright 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- 1-Methyl-4-phenylpyridinium toxicity
Animals
Brain drug effects
Brain pathology
Cell Line
Disease Models, Animal
Humans
Leupeptins toxicity
Lewy Bodies pathology
Mice
Oxidopamine toxicity
Parkinson Disease pathology
Rats
Solubility
Brain metabolism
Lewy Bodies metabolism
Parkinson Disease metabolism
Protein Kinases metabolism
Ubiquitin-Protein Ligases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 393
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 20171192
- Full Text :
- https://doi.org/10.1016/j.bbrc.2010.02.090