[Advances in the genetic studies in Parkinson's disease].
Genetic contribution to the etiology of Parkinson's disease (PD) is generally accepted based on the studies of the familial form of the disease and progress in molecular genetic techniques. To date, specific mutations have been identified in five separate genes and several chromosomal loci have been linked for different forms of familial parkinsonism. The discovery of alpha-synuclein, ubiquitin C-terminal hydrolase, parkin, tau and DJ-1 mutations and analysis of the biochemical and molecular properties of these gene products point to the critical role of protein aggregation in dopaminergic neurons of the substantia nigra as the basic mechanism leading to neurodegeneration also in sporadic form of the disease. Lewy bodies, even in sporadic PD, contain some of these gene products, particularly abundant fibrillar alpha-synuclein. Studies of familial parkinsonism provide evidence that PD is genetically heterogeneous. Evidence elucidated from genetic studies in PD suggests that parkinsonism is a complex disorder in which multiple gene-gene and gene-environment interactions play a critical role in the development of the disease and phenotypic variability. Further genetic studies in familial parkinsonism will enhance our knowledge of pathogenesis of PD and allow the development of neuroprotective treatments of PD and perhaps other forms of parkinsonism as well.
Klinika Neurologii, Collegium Medicum, Uniwersytet Jagielloński w Krakowie. krygowska@neuro.cm-uj.krakow.pl
Anna
A
Krygowska-Wajs
Zbigniew
Z
Wszolek
D004027:Diencephalon / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016631:Lewy Bodies / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D000071617:Protein Deglycase DJ-1; D051843:Synucleins; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein
D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D043222:Ubiquitin Thiolesterase