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Neurosci Lett. 2001 Jan 19;297(3):191-4.

Proteasomal function is impaired in substantia nigra in Parkinson's disease.

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  • 1Neurodegenerative Disease Research Centre, Division of Pharmacology and Therapeutics, Guy's, King's and St. Thomas' School of Biomedical Sciences, Hodgkin Building, King's College, Guy's Campus, SE1 1UL, London, UK.

Abstract

The accumulation of alpha-synuclein, ubiquitin and other proteins in Lewy bodies in degenerating dopaminergic neurones in substantia nigra in idiopathic Parkinson's disease (PD) suggest that inhibition of normal/abnormal protein degradation may contribute to neuronal death. We now show for the first time that the chymotrypsin- (39%), trypsin- (42%) and postacidic-like (33%) hydrolysing activities of 20/26S proteasome are impaired in substantia nigra in PD. Proteasome inhibition does not appear to result from drug treatment since high concentrations of L-3,4-dihydroxyphenylalanine had no effect on enzymatic activity in vitro. These observations provide the first direct evidence that inhibition of the ubiquitin-proteasome pathway leading to altered protein handling and Lewy body formation may be responsible for degeneration of the nigrostriatal pathway in idiopathic PD.

PMID:
11137760
[PubMed - indexed for MEDLINE]
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