Shimshek, Derya, Schweizer, Tatjana, Schmid, Peter and Van Der Putten, P. Herman (2012) Excess α-synuclein worsens disease in mice lacking ubiquitin carboxy-terminal hydrolase L1. Scientific Reports, 262 (2). ISSN 2045-2322

Abstract

Mutations in α-synuclein (αSN) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have been linked to familial Parkinson’s disease (PD). Physical and functional interactions between these two proteins have been described. Whether they act additively in vivo to influence disease has remained controversial. αSN is a presynaptic protein and the major constituent of Lewy inclusions, histopathological hallmarks of PD. UCH-L1 regulates ubiquitin stability in the nervous system and its loss results in neurodegeneration in peripheral and central neurons. Here, we used genetics to show that UCH-L1-deficiency together with excess α-synuclein worsen disease. Double mutant mice show earlier-onset motor deficits, a shorter lifespan and forebrain astrogliosis but the additive disease-worsening effects of UCH-L1-deficiency and excess αSN are not accompanied by microgliosis, ubiquitin pathology or changes in pathological αSN protein levels and species.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/pubmed?term=...
Related URLs:	http://www.ncbi.nlm.nih.gov/pubmed?term=...
Date Deposited:	13 Oct 2015 13:14
Last Modified:	13 Oct 2015 13:14
URI:	https://oak.novartis.com/id/eprint/6545