Parkinson’s Disease I: Degeneration and Dysfunction of Dopaminergic Neurons

Abstract

Parkinson disease (PD) is the second most common progressive neurodegenerative disorder, with a prevalence of approximately 1–2% at the age of 65. PD is due to the relatively selective loss of dopaminergic neurons in the substantia nigra pars compacta, which leads to a profound reduction in striatal dopamine (DA). There is growing recognition that (PD) is likely to arise from the combined effects of genetic predisposition as well as largely unidentified environmental factors. Although responsible for only a small minority of cases of PD, recently identified genetic mutations have provided tremendous insights into the basis for neurodegeneration and have led to growing recognition of the importance of abnormal protein handling in Parkinson’s as well as other neurodegenerative disorders. The mutant gene products all cause dysfunction of the ubiquitin-proteosome system, identifying protein modification and degradation as critical for pathogenesis. A number of environmental factors are known to be toxic to the substantia nigra. We review the various genetic and environmental factors thought to be involved in PD, as well as the mechanisms that contribute to degeneration of dopaminergic neurons in PD.