Potential role of α-synuclein in neurodegeneration: studies in a rat animal model.

摘要

Experimental models suggested to shed light on the neuro-pathobiology of Parkinson's disease (PD) and related disorders come from essentially four sources: pharmacological, e.g., reserpin or toxic, like MPTP (Meredith and Rademacher 2011); rotenone and paraquat (Nistico et al. 2011), genetic (Corti et al. 2011), and cellular (Albedo et al. 2012). Over the last few years, a myriad of different models carrying mutations similar to those found in humans in Drosophila melanogaster (Whitworth 2011), Caenorhabditis Elegans, and rodents (Stoica et al. 2012) have been developed to study the pathogenesis of these diseases. Although some genetic models reproduced the key features of PD, including dopaminergic neurodegeneration, they did not succeed in reproducing both the pathology and progressive degenerating process in human PD (Blesa et al. 2012). Viral PD models comprising aSyn and LRRK-2-based over-expression or mimicking parkin loss of function by over-expression of parkin substrates (Low and Aebischer 2011) may also provide valuable insights into PD mechanisms. However, there is a lack of spontaneous inherited animal models that show movement disorder phenotype and recapitulate all or even most of the end-stage pathological features of human PD.