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Neurosci Lett. 2002 Jul 5;326(3):155-8.

Selective loss of 20S proteasome alpha-subunits in the substantia nigra pars compacta in Parkinson's disease.

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  • 1Department of Neurology, Mount Sinai School of Medicine, Annenberg 14-73, One Gustave L. Levy Place, New York, NY 10029, USA. kevin.mcnaught@mssm.edu

Abstract

The proteolytic activities of 26/20S proteasomes are impaired in the substantia nigra pars compacta (SNc) in sporadic Parkinson's disease (PD). In the present study, we examined the structural integrity of the proteasome by determining the levels of the beta- and alpha-subunits which together normally constitute the catalytic core of 26/20S proteasomes. Western blot analyzes and immunohistochemical staining revealed a major and selective loss of alpha-subunits in dopaminergic neurons of the SNc but not in other brain regions in sporadic PD. This defect is known to cause the proteasome to become unstable and prevents its assembly with resultant impairment of enzymatic activity. Thus, structural and function defects in 26/20S proteasomes may underlie protein accumulation, formation of proteinaceous Lewy bodies and dopaminergic neuronal death in the SNc in sporadic PD.

PMID:
12095645
[PubMed - indexed for MEDLINE]
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