@article{acfe3898170e4e9281cc15ce36115a85,
title = "Parkin: Clinical aspects and neurobiology",
abstract = "A variety of mutations in parkin are linked to autosomal recessive Parkinson's disease (PD). Mutations in parkin may be one of the most common causes of autosomal recessive PD. Parkin is an E3 ubiquitin-protein ligase and familial associated mutations disrupt the E3 ligase activity, thus implicating derangements in the ubiquitin proteasomal pathway in the pathogenesis of PD. We review the clinical and neuropathological features of Parkinson's disease caused by parkin mutations. In addition, we discuss the emerging evidence that parkin is an E3 ubiquitin-protein ligase and how derangements in its E3 ligase activity might cause autosomal recessive PD.",
keywords = "Dopamine, Neurodegeneration, Proteasome, UCHL-1, Ubiquitin, Ubiquitinization, α-Synuclein",
author = "Yi Zhang and Dawson, {Valina L.} and Dawson, {Ted M.}",
note = "Funding Information: The unfolded protein response is part of the cellular response to the endoplasmic reticulum (ER) stress. The ER contains a protein quality control system that discovers misfolded or unassembled secretory proteins and subjects them to degradation in the cytosol. A variety of situations can induce ER stress, including oxidative stress, which has been widely believed to play a central role in the pathogenesis of PD [78] . The common result of these insults results in the unfolded protein exceeding the capacity of the ER machinery to deal with them. Upon unfolded protein response, expression of a variety of genes are up regulated, including genes involved in the ER-associated protein degradation (ERAD) pathway. Misfolded proteins are retrotranslocated from the ER back to cytosol and are subsequently degraded by the ubiquitin-proteasome system. Imai et al. hypothesized that parkin might be one of the E3 ligases involved in the ERAD system [71] . The deletion of the parkin gene may lead to accumulation of misfolded substrate protein(s) in the ER, which in turn results in the nigral cell death that causes AR-JP. This hypothesis is partially supported by the subcellular localization of parkin in the microsomal fraction [52] . Furthermore, ultrastructural studies also showed that parkin is located in the ER [53,57] . Thus, the study by Imai et al. provides a new avenue of investigation into the functional characterization of parkin. It will be important to know whether parkin could also protect dopamingeric neurons from ER stress inducing stimuli. ",
year = "2001",
month = dec,
doi = "10.1016/S1566-2772(01)00025-1",
language = "English (US)",
volume = "1",
pages = "467--482",
journal = "Clinical Neuroscience Research",
issn = "1566-2772",
publisher = "Elsevier BV",
number = "6",
}