J Korean Neurol Assoc.  2004 Oct;22(5):421-432.

Etiology and Pathogenesis of Parkinson's Disease

• Kim YJ

Abstract

Efforts to find etiologies and understand pathogenesis of Parkinson's disease (PD) have progressed over decades from epidemiological studies or biochemical studies on brain tissues of PD to discovering genes responsible for familial Parkinson's diseases and dissecting their roles and mechanisms in dopaminergic neuronal death at the molecular level. Eleven loci have been identified in familial PD and five genes have cloned. Although diverse genetic and environmental factors were identified, mechanisms of neurodegeneration by these etiological factors converge into four basic mechanisms; oxidative stress, mitochondrial complex I dysfunction, impairment of ubiquitin-proteasome pathway, and accumulation and aggregation of misfolded/unfolded proteins. These mechanisms appear to be closely interconnected with each other and lead to complex downstream cell death machineries. Understanding more sophisticated pathogenesis of dopaminergic neuronal death will help elucidating critical steps in dopaminergic cell death and developing therapeutic agents in the future.

Keyword

Parkinson's disease; Mitochondrial; Oxidative stress; Proteasome; Aggregation

MeSH Terms

Brain
Cell Death
Clone Cells
Dopaminergic Neurons
Oxidative Stress
Parkinson Disease*
Proteasome Endopeptidase Complex
Proteasome Endopeptidase Complex