Vesicular Integrity in Parkinson’s Disease

  • Shawn P. Alter
  • Gina M. Lenzi
  • Alison I. Bernstein
  • Gary W. Miller
Movement Disorders (SA Factor, Section Editor)

DOI: 10.1007/s11910-013-0362-3

Cite this article as:
Alter, S.P., Lenzi, G.M., Bernstein, A.I. et al. Curr Neurol Neurosci Rep (2013) 13: 362. doi:10.1007/s11910-013-0362-3
Part of the following topical collections:
  1. Topical Collection on Movement Disorders

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.

Keywords

DopamineVesicleTransportVMAT2Parkinson’s disease

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shawn P. Alter
    • 1
  • Gina M. Lenzi
    • 2
  • Alison I. Bernstein
    • 1
  • Gary W. Miller
    • 3
    • 4
    • 5
  1. 1.Department of Environmental Health, Rollins School of Public HealthEmory UniversityAtlantaUSA
  2. 2.Department of Biochemistry, School of MedicineEmory UniversityAtlantaUSA
  3. 3.Department of Neurology, School of MedicineEmory UniversityAtlantaUSA
  4. 4.Department of Pharmacology, School of MedicineEmory UniversityAtlantaUSA
  5. 5.Department of Environmental HealthRollins School of Public HealthAtlantaUSA