New aspects of genetic contributions to Parkinson's disease.
Over the last few years, several genes for rare, monogenically inherited forms of Parkinson's disease (PD) have been mapped and/or cloned. In dominant families, mutations have been identified in the gene for alpha-synuclein. Aggregation of this protein in intracellular inclusions (Lewy bodies) may be crucial in the molecular pathogenesis of the disease. Three genes have been identified to cause autosomal-recessive early-onset parkinsonism: parkin, DJ1, and PINK1. These genes are thought to be involved in the proteasomal protein degradation pathway, in the cell's response to oxidative stress, and in mitochondrial function, respectively. It is therefore concluded that these cellular mechanisms may play an important role in the degenerative process of PD. There is also accumulating evidence that genetic factors play a role in the common sporadic form of PD, however their precise nature remains unknown.
Hofer
Anne
A
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tuebingen, 72076 Tuebingen, Germany.
Gasser
Thomas
T
D000818:Animals; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics*; D051843:Synucleins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D046988:Proteasome Endopeptidase Complex; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D051843:Synucleins; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C111567:parkin protein; C105131:PARK7 protein, human