Genetic Animal Models of Parkinson's Disease

被引:656
作者
Dawson, Ted M. [1 ,2 ,3 ,5 ]
Ko, Han Seok [1 ,2 ,3 ]
Dawson, Valina L. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, NeuroRegenerat Program, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Programs, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA
关键词
HUMAN ALPHA-SYNUCLEIN; DOPAMINERGIC NEURON DEGENERATION; UBIQUITIN-PROTEIN LIGASE; DROSOPHILA DJ-1 MUTANTS; TRANSGENIC MICE; OXIDATIVE STRESS; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; CAENORHABDITIS-ELEGANS; KINASE-ACTIVITY;
D O I
10.1016/j.neuron.2010.04.034
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the degeneration of dopamine (DA) and non-DA neurons, the almost uniform presence of Lewy bodies, and motor deficits. Although the majority of PD is sporadic, specific genetic defects in rare familial cases have provided unique insights into the pathogenesis of PD. Through the creation of animal and cellular models of mutations in LRRK2 and a-synuclein, which are linked to autosomal-dominant PD, and mutations in parkin, DJ-1, and PINK1, which are responsible for autosomal-recessive PD, insight into the molecular mechanisms of this disorder are leading to new ideas about the pathogenesis of PD. In this review, we discuss the animal models for these genetic causes of PD, their limitations, and value. Moreover, we discuss future directions and potential strategies for optimization of the genetic models.
引用
收藏
页码:646 / 661
页数:16
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