Genetic Animal Models of Parkinson’s Disease

By T. Dawson, H. Ko, Valina L. Dawson. Neuron, 2010

818 citations recorded by the source corpus.

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 α-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.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/b9a730834598db0751e1abb923ee52ca28fda4a7

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Citations in the corpus

Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control (2014, background): “The deterioration of these mechanisms has been hypothesized to underlie the pathogeneses of several neurodegenerative diseases, most notably Parkinson’s disease (PD), the second-most common neurodegenerative disorder worldwide (Tatsuta & Langer, 2008; Dawson et al, 2010; Schon & Przedborski, 2011).”
PARIS (ZNF746) Repression of PGC-1α Contributes to Neurodegeneration in Parkinson’s Disease (2011, neutral): “A number of reasons were recently put forward regarding the lack of overt degeneration of DA neurons in genetic animal models of PD including compensatory mechanisms (Dawson et al., 2010).”
Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, neutral): “…alterations, oxidative stress, and impaired clearance of misfolded proteins and damaged orga-* nelles by proteasomal and lysosomal degradation pathways contribute to the disease process (reviewed in Dawson et al , 2010; Corti et al , 2011; Martin et al , 2011; and Shulman et al , 2011).”
Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease (2011, background): “Attempts to produce a-synuclein knockouts, over-expressers and transgenics led to a variety of abnormalities in the brain and spinal cord, including mitochondrial abnormalities, gliosis, loss of motor neurons, a-synuclein aggregate formation and some functional abnormalities in the nigro-striatal sy”
Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice (2012, neutral): “Moreover, despite the observation that α-Syn pathology is present in virtually all sporadic and familial PD patients (4) and that its distribution correlates with clinical symptoms (5–7), the precise relationship between α-Syn misfolding and DA neuron loss remains controversial because neither trans”
Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations (2011, neutral): “However, cellular and transgenic animal models expressing such mutants only partially recapitulate PD pathology (Dawson et al., 2010).”