Neural and immune mechanisms in the pathogenesis of Parkinson's disease

J Neuroimmune Pharmacol. 2013 Mar;8(1):189-201. doi: 10.1007/s11481-013-9435-y. Epub 2013 Feb 3.


Although almost 50 years have passed since impaired dopaminergic transmission was identified as the main neurochemical defect in Parkinson's disease (PD), the cause of the disease remains unknown. A restricted number of biological mechanisms are likely to contribute to the process of cell death in the nigrostriatal pathway. These mechanisms include mitochondrial defects and enhanced formation of reactive oxygen species--leading to oxidative damage--and abnormal protein aggregation. In addition to or, possibly, intermingled with these mechanisms of neuronal damage there is another crucial factor: neuroinflammation. The inflammatory response associated with cell loss in the dopaminergic nigrostriatal tract and, more in general, the role of immune mechanisms are increasingly recognized in PD pathogenesis. Neuroinflammatory changes have been repeatedly demonstrated, in both neurotoxic and transgenic animal models of PD, as well as in PD patients. Transgenic models based on α-synuclein overexpression, in particular, have provided crucial insights into the correlation between this protein and the dichotomous response that microglia can activate, with the polarization toward a cytotoxic (M1) or cytoprotective (M2) phenotype. Full understanding of such mechanisms may set the ground for a fine tuning of the neuroinflammatory process that accompanies and sustains neurodegeneration, thereby opening new therapeutic perspectives for PD.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / immunology
  • Adaptive Immunity / physiology
  • Animals
  • Disease Models, Animal
  • Humans
  • Immunity, Innate / immunology
  • Immunity, Innate / physiology
  • Mitochondrial Diseases / pathology
  • Mitochondrial Diseases / physiopathology
  • Nervous System / immunology*
  • Nervous System / pathology*
  • Nervous System / physiopathology
  • Neuritis / pathology
  • Neuroimmunomodulation / physiology
  • Oxidative Stress / physiology
  • Parkinson Disease / immunology*
  • Parkinson Disease / pathology*
  • Parkinson Disease / physiopathology
  • alpha-Synuclein / metabolism
  • alpha-Synuclein / physiology


  • alpha-Synuclein