背景:用于帕金森病药物发现和开发的动物模型在表征疾病的病理生理学和相关损伤机制方面发挥了重要作用。药物靶标鉴定,以及新型治疗剂的毒性/安全性评估,药代动力学,药效学,和功效。
目标:审查旨在改革范围,优势,以及各种帕金森病模型的局限性及其在转化研究中的范围。PD动物模型缺乏黄金标准是设计验证系统的主要挑战。本文试图为PD动物模型的研究提供一种验证方法。
方法:因为潜在的疾病机制在不同物种之间是如此相似,可以使用动物模型推断帕金森病研究的结果。此外,用于访问神经行为测试的行为测试及其局限性被探索用于啮齿动物,非人灵长类动物,低级动物,和无脊椎动物。性别选择性和非选择性的作用是审查中解决的PD模型验证中的一个主要问题。
结果:根据与人类状态的比较,对帕金森病(PD)的动物模型进行了严格的验证。关于PD的毒理学和安全性调查,非动物选项必须经过彻底验证。使用帕金森病动物模型作为概念验证研究既有优点也有缺点。
结论:为要测试和开发的给定药物选择的特定动物模型取决于特定研究的目标。
BACKGROUND: Animal models for drug discovery and development in Parkinson \'s disease have played an important role in the characterization of the pathophysiology of diseases and associated mechanisms of injury, drug target identification, and evaluation of novel therapeutic agents for toxicity/ safety, pharmacokinetics, pharmacodynamics, and efficacy.
OBJECTIVE: The review is intended to reform the scope, advantages, and limitations of various Parkinson\'s Disease models and their scope in translational research. The lack of a gold standard for PD animal models presents a major challenge in devising a validation system. This review is an attempt to provide a way to adopt the validation approach for PD animal model for research.
METHODS: Because underlying disease mechanisms are so similar across species, it is possible to extrapolate results from Parkinson\'s disease studies using animal models. Furthermore, behavioural tests used to access the neurobehavioral test with its limitations were explored for rodents, non-human primates, lower-order animals, and invertebrates. The role of gender selectivity and non-selectivity is the one major concern in PD model validation that is addressed in the review.
RESULTS: The rigorous validation has been done on animal models for Parkinson\'s disease (PD) based on comparisons to the human state. Regarding toxicological and safety investigations in PD, non-animal options must be thoroughly validated. There are both advantages and disadvantages to using animal models of Parkinson\'s disease as proof-of-concept research.
CONCLUSIONS: The specific animal model selected for a given drug to be tested and developed depends on the goal of the specific study.