Molecular pathways of neurodegeneration in Parkinson's disease

Parkinson’s disease (PD) is a complex disorder with many different causes, yet they may intersect in common pathways, raising the possibility that neuroprotective agents may have broad applicability in the treatment of PD. Current evidence suggests that mito-chondrial complex I inhibition may be the central cause of sporadic PD and that derangements in complex I cause -synuclein aggregation, which contributes to the demise of dopamine neurons. Accumulation and aggregation of -synuclein may further contribute to the death of dopamine neurons through impairments in protein handling and detoxification. Dysfunction of parkin (a ubiquitin E3 ligase) and DJ-1 could contribute to these deficits. Strategies aimed at restoring complex I activity, reducing oxidative stress and -synuclein aggregation, and enhancing protein degradation may hold par-ticular promise as powerful neuroprotective agents in the treatment of PD. PD is the most common neurodegenerative movement disorder. It affects more than 0.1 % of the population older than 40 years of age (1). Clinically, most patients present with a motori