Pathogenesis of Parkinson's disease: prospects of neuroprotective and restorative therapies

Mol Neurobiol. 2004 Feb;29(1):15-30. doi: 10.1385/MN:29:1:15.

Abstract

Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons of substantia nigra projecting to striatum. The cause of idiopathic PD is obscure, and most cases are sporadic. It is widely accepted that there is a genetic component of the disease, and the earlier the age of onset, the greater the likelihood that genetic factors play a dominant role. Oxidative stress of the substantia nigra seems to contain the driving force for neurodegeneration, leading to a destructive "toxic cycle." The most prevalent therapy is levodopa administration, but it is not efficacious after several years of treatment. Several alternative therapies are currently being explored, such as neuroprotective approaches. Compounds with potentially neuroprotective efficacy such as selegiline, dopamine agonists, riluzole, creatine, and coenzyme Q10 are currently being tested. Trophic factors represent another class of neuroprotective compounds, but their intracerebral administration is difficult to achieve. In this respect, a potentially useful therapeutic approach is grafting cell vectors that release trophic molecules that stimulate regeneration in the damaged nigrostriatal system. Promising results have been obtained with fibroblasts engineered to secrete glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) or viral vectors expressing GDNF. We have tested the suitability of intrastriatal grafts of chromaffin cells obtained from the Zuckerkandl's organ, which exert beneficial effects in parkinsonian rats, and release trophic factors such as GDNF and transforming growth factor-beta1 (TGF-beta1).

Publication types

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

MeSH terms

  • Animals
  • Cell Transplantation / trends*
  • Genetic Therapy / methods
  • Genetic Therapy / trends
  • Humans
  • Nerve Growth Factors / biosynthesis
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Parkinson Disease / etiology*
  • Parkinson Disease / physiopathology
  • Parkinson Disease / therapy*

Substances

  • Nerve Growth Factors
  • Neuroprotective Agents