Genetics of Parkinson's disease and parkinsonism.
The past 10 years has seen a shift in our etiological concepts of Parkinson's disease, moving from a nearly exclusively environmentally mediated disease towards a complex disorder with important genetic contributors. The identification of responsible mutations in certain genes, particularly alpha-synuclein, Parkin, PINK1, DJ-1 and LRRK2, has increased our understanding of the clinical and pathological changes underlying Parkinson's disease, with implications for patient diagnosis, management and future research. This review will outline the specific genetic advances, discuss their implications for clinical practice and hint at future directions for research into this common and disabling disease.
Douglas
Michael R
MR
University of Birmingham Medical School, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK. m.r.douglas@blueyonder.co.uk
Lewthwaite
Alistair J
AJ
Nicholl
David J
DJ
D001921:Brain / Q000378:metabolism*; D002986:Clinical Trials as Topic / Q000639:trends; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000517:prevention & control; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human