TY - JOUR
T1 - Value of genetic models in understanding the cause and mechanisms of Parkinson's disease
AU - Moore, Darren J.
AU - Dawson, Ted M.
N1 - Funding Information:
The authors are grateful for grant support from the NIH, NINDS NS057795, NS05427, NS04826 NS038377, National Parkinson Foundation, Michael J. Fox Foundation for Parkinson’s Research, and the American Parkinson Disease Association. Dr. Dawson is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases at Johns Hopkins.
PY - 2008
Y1 - 2008
N2 - 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 α-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, α-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.
AB - 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 α-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, α-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.
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U2 - 10.1007/s11910-008-0045-7
DO - 10.1007/s11910-008-0045-7
M3 - Article
C2 - 18590612
AN - SCOPUS:53449093161
SN - 1528-4042
VL - 8
SP - 288
EP - 296
JO - Current neurology and neuroscience reports
JF - Current neurology and neuroscience reports
IS - 4
ER -