Mitochondrial dysfunction in Parkinson's disease.
This review discusses the etiology and pathogenesis of Parkinson's disease (PD). Mitochondrial respiratory failure and oxidative stress appear to be two major contributors to nigral neuronal death in PD. Complex I deficiency has been reported by several groups and appears to be one of the basic abnormalities responsible for mitochondrial failure. The principal question is whether or not complex I deficiency is primary or secondary. The second question is whether or not complex I deficiency is localized in the nigrostriatal system or is systemically present. It is our impression that complex I deficiency is not the primary cause but that its deficiency appears to be systemic. The primary cause may be the combination of genetic background and potential nigral neurotoxins. Exposure of nigral neurons to a high risk for oxidative damage because of its high dopamine content may be the reason for more pronounced nigral complex I deficiency compared to systemic organs. Oxidative stress and mitochondrial failure produce a vicious cycle in nigral neurons. To explore the genetic risk factors of sporadic PD, studies on familial PD and parkinsonism are important. Recently, an autosomal dominant form of familial PD was found to be caused by point mutations of the alpha-synuclein gene, and an autosomal recessive familial parkinsonism was mapped to the long arm of chromosome 6 near the Mn-SOD gene locus. Information obtained in these familial cases will contribute to the research on sporadic PD.
Mizuno
Y
Y
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
Yoshino
H
H
Ikebe
S
S
Hattori
N
N
Kobayashi
T
T
Shimoda-Matsubayashi
S
S
Matsumine
H
H
Kondo
T
T
D002467:Cell Nucleus / Q000235:genetics; D005815:Genetic Code; D015894:Genome, Human; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency*; D009498:Neurotoxins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000209:etiology / Q000503:physiopathology*
D009498:Neurotoxins; D016660:NAD(P)H Dehydrogenase (Quinone)