6-hydroxydopamine as preclinical model of parkinson's disease

Abstract

Like many other diseases, Parkinson's disease (PD) requires preclinical models to understand the underlying molecular and cellular mechanisms that cause the disorder. Such models will also help to identify novel potential drug targets and to elucidate the effects of new drug candidates. The hydroxylated analogue of dopamine, 6-hydroxydopamine (6-OHDA), has been exploited as an experimental model to study PD. It also has been used extensively as a test system for novel symptomatic agents and for assessment of neuroprotective and neurorepair strategies. The 6-OHDA lesioned rat appears to be a good predictor for monitoring the efficacy of new dopaminergic drugs that enter phase II/In clinical trials. The aim of this chapter is the molecular and cellular mechanisms that are involved in the preclinical model of Parkinson's disease based on 6-OHDA. With special attention, we address the role of second messengers as the role of reactive oxygen species and the mitochondria as the headquarters of cell death. The role of molecular signaling pathways, for instance, the participation of Bcl-2 family members, will also be addressed.