Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/17523
Title: Understanding how mutations and stress factors contribute to Parkin dysfunction - Implications for Parkinson's disease
Authors: WANG CHENG
Keywords: Parkinson's Disease; parkin; mutations; solubility; aggregation; PD-linked stressors
Issue Date: 9-Oct-2007
Source: WANG CHENG (2007-10-09). Understanding how mutations and stress factors contribute to Parkin dysfunction - Implications for Parkinson's disease. ScholarBank@NUS Repository.
Abstract: Parkin dysfunction represents not only a predominant cause of familial parkinsonism but also a formal risk factor for sporadic form of Parkinsona??s disease (PD). However, how parkin becomes dysfunctional was not well understood. In this study, I found that mutations in parkin do not typically impair its catalytic competency but instead frequently alter the protein solubility and promote its intracellular aggregation. I also found that a wide variety of PD-linked stressors induce parkin solubility alterations and promote its aggregation within the cell, suggesting a mechanism for parkin dysfunction in the pathogenesis of idiopathic PD. More recently, I demonstrated that select parkin mutations could exert dominant effects over the wild-type protein in vivo, thus supporting emerging evidence suggesting that heterozygous parkin mutations may be pathogenic. Taken together, these findings contribute significantly to our understanding of the contributors to parkin dysfunction and provide important sights into the pathogenesis of PD.
URI: http://scholarbank.nus.edu.sg/handle/10635/17523
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Wang Cheng ht027316m.pdf9.17 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

212
checked on Dec 11, 2017

Download(s)

139
checked on Dec 11, 2017

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.