Neuroprotective role of dopamine agonists: evidence from animal models and clinical studies

Abstract

Parkinson disease is a progressive neurodegenerative disease that affects, among other neurotransmitter systems, the nigrostriatal dopaminergic projection. Palliative treatment with levodopa and/or dopamine agonists improves motor symptoms even though patients continue to get clinically worse by the neurodegenerative process that continues to act as the major factor of physiological aging. Studies (in vitro and in vivo) with experimental models have shown that dopamine agonists have neuroprotective effects, directly or indirectly mediated by their ability to stabilize mitochondria, antioxidant effects, synthesis of growth factors, stabilization of the ubiquitin-proteasome system, activation of autophagy, antiapoptotic induction of Bcl2 family, or enhancement of neurogenesis (proliferation and migration) in the subventricular zone. Clinical studies have not completely confirmed these effects. Analysis in better characterized groups of patients with similar clinical symptoms, identical treatments, and the same evolution time are required. Technological advances which enable the learning of the etiology and the pathogenesis (genetic and environmental) of the disease, together with clinical assessment methods, bring hope to the development of new molecules in the symptomatic treatment of Parkinson disease. These molecules must display neuroprotective potential (prophylactic and/or therapeutic) which must be able to maintain the brain's physiological function and to modify or slow the natural course of the disease.