Potential neuroprotection mechanisms in PD: focus on dopamine agonist pramipexole

AbstractBackground:The death of dopaminergic neurons in Parkinson's disease (PD) appears to have various causes, including oxidative stress, excitotoxicity, mitochondrial dysfunction (and associated apoptosis), ubiquitin/proteasomal dysfunction, and inflammation, any of which could in principle be the therapeutic target of a neuroprotective drug. The biology of dopaminergic neurons offers further potential targets, involving neurotrophic factors, dopamine-neuron genes, and even neurogenesis.Objective:To outline each hypothetical neuroprotective mechanism, the evidence suggesting its relevance to PD, and the research on pharmacologic intervention.Methods:A PubMed search was conducted to identify relevant preclinical and clinical literature published between 1989 and 2009. Additional articles were identified by reviewing the reference lists of papers selected in the original search. To circumscribe the survey and facilitate consideration of the conditions required for a neuroprotective effect, emphasis was ...