Vesicular Integrity in Parkinson's Disease

• Type of Material: Article
• Authors: Shawn P. Alter, Emory University; Gina M. Lenzi, Emory University; Alison I. Bernstein, Emory University; Gary W Miller, Emory University
• Language: English
• Date: 2013-07
• Publisher: Springer (part of Springer Nature): Springer Open Choice Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Springer Science+Business Media New York 2013
• Final Published Version (URL): http://link.springer.com/article/10.1007%2Fs11910-013-0362-3
• Title of Journal or Parent Work: Current Neurology and Neuroscience Reports
• ISSN: 1528-4042
• Volume: 13
• Issue: 7
• Start Page: 362
• End Page: 362
• Grant/Funding Information: P01 ES016731, T32 ES012870, T32 GM008602, and T32 DA015040.
• Keywords: Transport; VMAT2; Vesicle; Parkinson’s disease; Dopamine
• Research Categories: Biology, Neuroscience; Health Sciences, Public Health; Biology, Cell

Abstract

The defining motor characteristics of Parkinson’s disease (PD) are mediated by the neurotransmitter dopamine (DA). Dopamine molecules spend most of their lifespan stored in intracellular vesicles awaiting release and very little time in the extracellular space or the cytosol. Without proper packaging of transmitter and trafficking of vesicles to the active zone, dopamine neurotransmission cannot occur. In the cytosol, dopamine is readily oxidized; excessive cytosolic dopamine oxidation may be pathogenic to nigral neurons in PD. Thus, factors that disrupt vesicular function may impair signaling and increase the vulnerability of dopamine neurons. This review outlines the many mechanisms by which disruption of vesicular function may contribute to the pathogenesis of PD. From direct inhibition of dopamine transport into vesicles by pharmacological or toxicological agents to alterations in vesicle trafficking by PD-related gene products, variations in the proper compartmentalization of dopamine can wreak havoc on a functional dopamine pathway. Findings from patient populations, imaging studies, transgenic models, and mechanistic studies will be presented to document the relationship between impaired vesicular function and vulnerability of the nigrostriatal dopamine system. Given the deleterious effects of impaired vesicular function, strategies aimed at enhancing vesicular function may be beneficial in the treatment of PD.