title: Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.
abstract: Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials.
authors: University de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France. erwan.bezard@u-bordeaux2.fr
authors: Erwan
authors: E
authors: Bezard
authors: Zhenyu
authors: Z
authors: Yue
authors: Deniz
authors: D
authors: Kirik
authors: Maria Grazia
authors: MG
authors: Spillantini
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000009:adverse effects; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases