Mitochondrial dysfunction and biogenesis in the pathogenesis of Parkinson's disease.
Parkinson's disease (PD) is a progressive neurological disorder marked by nigrostriatal dopaminergic degeneration and development of cytoplasmic aggregates known as Lewy bodies. The impact of this disease is indicated by the fact that mortality is two to five times as high among affected persons as among age-matched controls. However, the cause of PD is still unknown and no cure is available at present. Several biochemical abnormalities have been described in the brains of patients with PD, including oxidative stress and mitochondrial dysfunction. Recent identification of specific gene mutations that cause PD has further reinforced the relevance of oxidative stress and mitochondrial dysfunction in the familial and sporadic forms of the disease. The proteins that are reported to be related to familial PD-PTEN-induced putative kinase 1 (PINK1), DJ-1, alpha- synuclein, leucine-rich repeat kinase 2 (LRRK2), and, possibly, parkin-are either mitochondrial proteins or are associated with mitochondria, and all are involved in pathways that elicit oxidative stress or free radical damage. Mitochondria are continually exposed to reactive oxygen species and accumulate oxidative damage more rapidly than the rest of the cell. Therefore, Parkinson's disease has been suggested to be associated with mitochondrial dysfunction. Since mitochondria are the major intracellular organelles that regulate both cell survival and death, clarifying the involvement of mitochondrial dysfunction and biogenesis during the process of PD could provide treatment strategies that might successfully intervene in the pathogenesis and slow the progression of the disease.
Lin
Tsu-Kung
TK
Department of Neurology, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Niaosong Township, Kaohsiung County 833, Taiwan (R.O.C.).
Liou
Cha-Wei
CW
Chen
Shang-Der
SD
Chuang
Yao-Chung
YC
Tiao
Mao-Meng
MM
Wang
Pei-Wen
PW
Chen
Jin-Bor
JB
Chuang
Jiin-Haur
JH
D017209:Apoptosis; D004272:DNA, Mitochondrial / Q000235:genetics; D004298:Dopamine / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D001678:Organelle Biogenesis; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics
D004272:DNA, Mitochondrial; D004298:Dopamine