[Parkin and mitochondria].
Parkinson disease (PD) is the most common neurodegenerative disease, and the majority of PD cases involve the sporadic from of PD. Although the etiology of the sporadic form is unknown, mitochondrial dysfunction and oxidative stress are considered to play a prominent role in its pathogenesis. The discovery of the genes that are linked to the rare familial form of PD has provided crucial insights into the molecular mechanisms involved in the pathogenesis of PD. Recent findings implicate mitochondrial dysfunction associated with oxidative damage (mitochondrial pathway) and abnormal protein accumulation (ubiquitin/ proteosome pathway) as the key molecular mechanisms compromising dopaminergic neurons in familial PD. Mutations in Parkin, PTEN-induced kinase 1 (PINK1) and DJ-1 are found in autosomal recessive forms of PD. Recent studies on these genes suggest the central importance of mitochondrial dysfunction and oxidative stress in PD. The above mentioned 3 proteins may be biologically related to each other and may protect the mitochondria against oxidative stress and other harmful stimulations. In particular, parkin appears to be the most important factor that improves the mitochondrial dysfunction. In this review we focus on the mitochondria and parkin function. We also provide an overview of the most relevant findings in recent years.
Mitsui
Takao
T
Department of Clinical Research, National Hospital Organization, Tokushima National Hospital, Yoshinogawa, Tokushima 776-8585, Japan.
Kuroda
Yukiko
Y
Kaji
Ryuji
R
D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008928:Mitochondria / Q000235:genetics* / Q000502:physiology*; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C105131:PARK7 protein, human