Value of genetic models in understanding the cause and mechanisms of Parkinson's disease.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized pathologically by the degeneration of nigrostriatal pathway dopaminergic neurons and other neuronal systems and the appearance of Lewy bodies that contain alpha-synuclein. PD is generally a sporadic disease, but a small proportion of cases have a clear genetic component. Mutations have been identified in six genes that clearly segregate with disease in rare families with PD. Transgenic, knockout, and virus-based models of disease have been developed in rodents to further understand how these genes contribute to the pathogenesis of PD. In general, these animal models recapitulate many key features of the disease, including derangements in dopaminergic synaptic transmission, selective neurodegeneration, neurochemical deficits, alpha-synuclein-positive neuropathology, and motor deficits. However, a genetic model with all or most of these pathogenic features has proved difficult to create. In this article, we discuss these mammalian genetic models of PD and what they have revealed about the cause and mechanisms of this disease.
Moore
Darren J
DJ
Institute for Cell Engineering and Department of Neurology, Johns Hopkins University School of Medicine, 733 North Broadway, Broadway Research Building, Suite 711, Baltimore, MD 21205, USA. djmoore@jhmi.edu
Dawson
Ted M
TM
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020734:Parkinsonian Disorders / Q000209:etiology* / Q000235:genetics*; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein