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• W1497682746 abstract "Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting 2% of the world population over the age of 65. The most common clinical symptoms include muscle rigidity, resting tremor, bradykinesia and postural instability as a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The surviving neurons often show protein inclusions, known as Lewy bodies (LBs) and Lewy neurites, which are the pathological hallmarks of PD. Misfolded and aggregated a-syn is the main protein component of LBs, which can be found in both sporadic and familial forms of PD (Spillantini et al., 1997). Mutations in the SNCA gene, which encodes for a-syn, as well as duplication and triplication of the gene, are associated with familial forms of PD. The precise structure of a-syn is not known. Nevertheless, it is believed to display an intrinsically unfolded structure that may shift to a partially folded -helical conformation upon interaction with membranes (Zhu and Fink, 2003). Although the physiological role of a-syn is poorly understood, it is thought to be associated with synaptic function and plasticity, cell differentiation and vesicular trafficking (Klein and Lohmann-Hedrich, 2007). In LBs the majority of a-syn protein is phosphorylated (Fujiwara et al., 2002). Other described post-translational modifications of a-syn include oxidation, ubiquitylation, nitration, sumoylation and glycation. However, the exact role of post-translational modifications in a-syn function in both physiological and pathological conditions remains unclear. Besides a-syn mutations, several additional genetic loci were associated with familial forms of the disease (Table 11.1). For example, the PARK2 loci encodes for Parkin, an E3 ubiquitin ligase. Parkin protein mutations are thought to result in insufficient" @default.
• W1497682746 created "2016-06-24" @default.
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• W1497682746 creator A5087439679 @default.
• W1497682746 date "2012-02-16" @default.
• W1497682746 modified "2023-09-26" @default.
• W1497682746 title "Novel Molecular Therapeutics in Parkinson's Disease" @default.
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• W1497682746 doi "https://doi.org/10.1002/9781119967309.ch11" @default.
• W1497682746 hasPublicationYear "2012" @default.
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