Deficiency in striatal dopamine action: An omen for parkinson’s disease?

Lenard Lachenmayer, Zhenyu Yue

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Parkinson’s disease (PD) is characterized by the degeneration of the dopaminergic nigrostriatal pathway. The reduction of striatal dopamine following the loss of nigral dopamine neurons is believed to be responsible for the characteristic PD symptom of motor dysfunction. The remarkable alleviation of PD symptoms in patients with the treatment of Levodopa is compelling evidence for the significant role of dopamine in the pathogenesis of PD. While the importance of dopamine in regulating motor function is well documented, it is unclear how dopamine physiology is altered and what exactly causes the specific degeneration of dopamine neurons in PD. The available evidence from PET and SPECT imaging in human PD and characterization of animal models of PD, however, suggests aberrant activity of the dopaminergic nigrostriatal system as a pathogenic precursor to nigrostrital degeneration. This hypothesis falls in line with current studies in animal models that demonstrate the role of familial PD mutations in perturbing dopamine release and striatal synaptic plasticity and implicate the possible link of impaired presynaptic terminals of nigrostriatal projection to the degeneration of dopamine neurons. This commentary reviews the aforementioned emerging evidence that points to a future direction of PD etiology research and biomarker studies focused on the dysfunctional presynaptic terminals of nigrostriatal projections. Furthermore, we will discuss the oxidative stress of cytosolic dopamine, a controversial hypothesis that suggests neurotoxicity of dopamine and explains the selective degeneration of nigral dopamine neurons.

Original languageEnglish
Title of host publicationNeurochemistry
Subtitle of host publicationMolecular Aspects, Cellular Aspects and Clinical Applications
PublisherNova Science Publishers, Inc.
Number of pages12
ISBN (Electronic)9781617285455
ISBN (Print)9781607418313
StatePublished - 1 Jan 2010


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