Dysfunction of dopamine homeostasis: clues in the hunt for novel Parkinson's disease therapies

FASEB J. 2013 Jun;27(6):2101-10. doi: 10.1096/fj.12-226852. Epub 2013 Mar 5.

Abstract

Parkinson's disease is the second most common neurodegenerative disorder and, at present, has no cure. Both environmental and genetic factors have been implicated in the etiology of the disease; however, the pathogenic pathways leading to neuronal degeneration are still unclear. Parkinson's disease is characterized by the preferential death of a subset of neurons in the mesencephalon that use dopamine as neurotransmitter for synaptic communication. Dopamine is a highly reactive molecule that can lead to cytotoxicity if not properly stored and metabolized. Targeting any of the pathways that tightly control this neurotransmitter holds great therapeutic expectations. In this article we present a comprehensive overview of the cellular pathways that control dopamine fate and discuss potential therapeutic approaches to counteract or slow Parkinson's disease onset and progression.

Keywords: dopamine metabolism; dopaminergic pathways; neurotransmission; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiparkinson Agents / therapeutic use
  • Disease Progression
  • Dopamine / metabolism*
  • Drug Discovery
  • Homeostasis*
  • Humans
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / etiology
  • Parkinson Disease / metabolism*

Substances

  • Antiparkinson Agents
  • Dopamine