IMR Press / FBL / Volume 13 / Issue 10 / DOI: 10.2741/2973

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Proteomic identification of novel proteins associated with Lewy bodies
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1 Department of Human Genetics, the Center for Neurodegenerative Diseases
2 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322
3 Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322

*Author to whom correspondence should be addressed.

Academic Editor: Batia Kaplan

Front. Biosci. (Landmark Ed) 2008, 13(10), 3850–3856; https://doi.org/10.2741/2973
Published: 1 May 2008
(This article belongs to the Special Issue Protein deposition diseases: pathology and micro-analytical methods)
Abstract

The manifestation of Lewy bodies (LB) in the brain is a hallmark of Parkinson's disease. Here, we present a comprehensive analysis of protein elements in Lewy bodies by comparative mass spectrometry. Cortical LB inclusions were enriched by sucrose gradient centrifugation from postmortem brains, and a negative control sample was prepared from specimen without LB pathology. Whereas ~550 proteins were identified in the LB-enriched sample by mass spectrometry, quantitative comparison with the control sample revealed that ~40 proteins were co-enriched with α-synuclein, the major component in Lewy bodies. As expected, the list of proteins included previously reported constituents, such as those involved in protein folding, membrane trafficking and oxidative stress. More interestingly, we discovered in the LB-enriched sample several kinases (MAPKK1/MEK1, protein kinase C, and doublecortin-like kinase), a novel deubiquitinating enzyme (otubain 1), and numerous ubiquitin ligases (KPC and SCF). The proteomic studies provide enzyme candidates to investigate the regulation of α-synuclein and/or other LB proteins, which may contribute to the formation of Lewy bodies and the toxicity of α-synuclein in the related neurodegenerative disorders.

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