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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 | Citation: | 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) |
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