The impact of genetic research on our understanding of Parkinson's disease.
Until recently, genetics was thought to play a minor role in the development of Parkinson's disease (PD). Over the last decade, a number of genes that definitively cause PD have been identified, which has led to the generation of disease models based on pathogenic gene variants that recapitulate many features of the disease. These genetic studies have provided novel insight into potential mechanisms underlying the aetiology of PD. This chapter will provide a profile of the genes conclusively linked to PD and will outline the mechanisms of PD pathogenesis implicated by genetic studies. Mitochondrial dysfunction, oxidative stress and impaired ubiquitin-proteasome system function are disease mechanisms that are particularly well supported by genetic studies and are therefore the focus of this chapter.
Martin
Ian
I
NeuroRegeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dawson
Valina L
VL
Dawson
Ted M
TM
D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / 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; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human