In vivo alpha-synuclein overexpression in rodents: A useful model of Parkinson's disease?
- 23 August 2007
- journal article
- review article
- Published by Elsevier BV in Experimental Neurology
- Vol. 209 (1), 22-27
- https://doi.org/10.1016/j.expneurol.2007.08.006
Abstract
Mutations in alpha-synuclein were the first genetic defect linked to Parkinson's disease (PD). The relevance of alpha-synuclein to sporadic PD is strongly supported by the presence of alpha-synuclein aggregates in neurons of patients. This has prompted the development of numerous animal models based on alpha-synuclein overexpression, primarily through genetic methods in mice and viral transduction in rats. In mice, different promoters and transgenes lead to a wide variety of phenotypes accompanied by non-existent, late onset, or non-specific neurodegeneration. Rapid neurodegeneration, in contrast, is observed after viral transduction but is limited to the targeted region and does not mimic the broad pathology observed in the disease. Overall, each model reproduces a subset of features of PD and can be used to identify therapeutic targets and test disease-modifying therapies. The predictive value of all models of the disease, however, remains speculative in the absence of effective neuroprotective treatments for PD in humans.Keywords
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