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Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders

Author(s): Yun-Tzai C. Lee and Shang-Te D. Hsu*

Volume 18, Issue 7, 2017

Page: [733 - 745] Pages: 13

DOI: 10.2174/1389203717666160217143721

Price: $65

Abstract

Parkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with α-synuclein (αS), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCHL1 and PD in terms of loss of cellular functions or gain of cellular toxicity.

Keywords: UCH-L1, α-synuclein, Lewy bodies, Parkinson’s disease, ubiquitin, misfolding.

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