The pathogenesis of cell death in Parkinson's disease

Concepts of pathogenesis in Parkinson's disease (PD) have been based on attempts to understand the mechanisms responsible for nigral dopaminergic cell death. Pathogenesis has been proposed to involve oxidative and nitrative stress, excitotoxicity, inflammation, mitochondrial dysfunction, and altered proteolysis. These processes are considered to form a complex cascade of interrelated events that lead to neuron death by way of apoptosis. However, current views on pathogenic mechanisms in PD may not be as exact as commonly proposed. Future concepts of pathogenesis in PD need to incorporate events leading to the destruction of non-dopaminergic nuclei and to distinguish between primary factors that are responsible for disease initiation and secondary factors that contribute to disease progression. Importantly, there is a need to determine whether PD is a single illness with a common pathogenesis or a group of related illnesses with different pathogenic mechanisms. This is an essential step to understanding pathogenesis and is critical to the development of comprehensive neuroprotective approaches to treatment.