Authors: Snyder, Heather¹; Wolozin, Benjamin²

Source: Journal of Molecular Neuroscience, Volume 24, Number 3, October 2004 , pp. 425-442(18)

Publisher: Humana Press

Abstract:

Parkinson' disease (PD) is a multifactorial disease that appears to arise from the effects of both genetic and environmental influences. Pesticides and heavy metals are the principle environmental factors that appear to impact on PD. The known genetic factors include multiple genes that have been identified in related parkinsonian syndromes, as well as α-synuclein. Genes associated with either PD or Parkinson-related disorders include parkin, DJ-1, ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1), nuclear receptor-related factor 1, and α-synuclein. α-Synuclein is particularly notable because it aggregates readily and is the main component of Lewy bodies (LBs). Aggregated α-synuclein binds the proteasome and potently inhibits proteasomal activity. Because ubiquitin accumulates in LBs, and parkin and UCH-L1 also interact with the ubiquitin proteasomal system, proteasomal dysfunction is thought to contribute to the pathophysiology of PD. Increasing numbers of experiments suggest that neurotoxins might interact with α-synuclein or other Parkinson-related proteins to contribute to the pathophysiology of PD. Transgenic animal models overexpressing α-synuclein develop agedependent motor dysfunction and inclusions in the brain stem that contain α-synuclein. These models are very helpful in elucidating the pathophysiology of PD but do not completely recapitulate the disease process. The relationship between these transgenic models and PD is a subject of intense investigation.

Keywords: Synuclein; parkin; DJ-1; ubiquitin; mitochondria; transgenic models; protein aggregation; neuroprotection; neurotoxins

Document Type: Research article

DOI: http://dx.doi.org/10.1385/JMN:24:3:425

Affiliations: 1: Boston University School of Medicine, 715 ALbany Street, Room L-603, 02118-2526, Boston, MA, 2: Boston University School of Medicine, 715 ALbany Street, Room L-603, 02118-2526, Boston, MA, Email: bwolozi@lumc.edu

Publication date: 2004-10-01

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