Etiology and Pathogenesis of Parkinson's Disease

J Korean Neurol Assoc > Volume 22(5); 2004 > Article

Journal of the Korean Neurological Association 2004;22(5): 421-432.

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한림대학교 일송생명과학연구소, 한림대학교 의과대학 신경과학교실

Etiology and Pathogenesis of Parkinson's Disease

Yun Joong Kim

ILSONG Institute of Life Science, Department of Neurology, Hallym University College of Medicine, Anyang, Korea

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.Key Words: Parkinson's disease, Mitochondrial, Oxidative stress, Proteasome, Aggregation