Genetic Models of Familial Parkinson's Disease

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

This chapter reviews vertebrate α-synuclein transgenic mouse models which have led to substantial advances in understanding the role of α-synuclein in pathogenic processes that are relevant to Parkinson's disease (PD). Mutations in the gene coding for leucine rich repeat kinase-2 (LRRK2) also lead to autosomal-dominant PD. LRRK2 is a large protein containing multiple functional domains including a GTPase and kinase domain. Of the various α-synuclein transgenic mice that have been generated over the years, the models using the murine Thy-1 promoter and the murine prion promoter recapitulate most if not all the pathogenic features of PD, except for degeneration of dopamine neurons. Transgenic mice overexpressing α-synuclein under either promoter develop α-synucleinopathy in neurons and overlapping brain regions with predominate pathology in spinal motor neurons, deep cerebellar nuclei, pontine reticular nuclei and the red nucleus. The neuronal populations are particularly vulnerable to α-synuclein-induced neurodegeneration in mice. It is suggested that the α-synuclein transgenic models can be used to explore the molecular basis of cell death induced by α-synuclein.

Original languageEnglish (US)
Title of host publicationParkinson's Disease
PublisherElsevier Inc.
Pages225-236
Number of pages12
ISBN (Print)9780123740281
DOIs
StatePublished - 2008

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Synucleins
Genetic Models
Parkinson Disease
Transgenic Mice
Phosphotransferases
Leucine
Red Nucleus
Cerebellar Nuclei
Prions
GTP Phosphohydrolases
Dopaminergic Neurons
Motor Neurons
Vulnerable Populations
Vertebrates
Cell Death
Pathology
Neurons
Mutation
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Genetic Models of Familial Parkinson's Disease. / Ying, Mingyao; Dawson, Valina; Dawson, Ted M.

Parkinson's Disease. Elsevier Inc., 2008. p. 225-236.

Research output: Chapter in Book/Report/Conference proceedingChapter

Ying, Mingyao ; Dawson, Valina ; Dawson, Ted M. / Genetic Models of Familial Parkinson's Disease. Parkinson's Disease. Elsevier Inc., 2008. pp. 225-236
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