Is there a pathogenic role for mitochondria in Parkinson's disease?
Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause. For decades, a deficit in mitochondrial respiration was thought to be a key factor in PD neurodegeneration. However, excluding a few exceptions where a clinical picture of parkinsonism is associated with a mitochondrial DNA mutation, preclinical and clinical studies have failed to identify any genetic mutations in the genes encoding for the electron transport chain complexes in PD patients. More recently, it has been discovered that mutations in the genes encoding for Parkin, PINK1 and DJ1 are associated with familial forms of PD and with mitochondrial alterations, including morphological abnormalities. These results have led many researchers to revisit the question of mitochondrial biology as a primary mechanism in PD pathogenesis, this time from an angle of perturbation in mitochondrial dynamics and not from the angle of a deficit in respiration.
Vives-Bauza
Cristofol
C
Department of Neurology, Columbia University, New York, New York 10032, USA.
de Vries
Rosa L A
RL
Tocilescu
Maja Aleksandra
MA
Przedborski
Serge
S
D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000150:complications* / Q000235:genetics; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
D004272:DNA, Mitochondrial; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C105131:PARK7 protein, human