Department of Pharmacology, ISF College of Pharmacy, Moga 142001, Affiliated to I.K Gujral Punjab Technical University, Jalandhar, Punjab, India.
Department of Pharmaceutical Sciences, HNB Garhwal University (A Central University), Chauras Campus, Distt. Tehri Garhwal, Uttarakhand 246174, India.
Behav Brain Res. 2024 Feb 29;459:114757. doi: 10.1016/j.bbr.2023.114757. Epub 2023 Nov 11.
Huntington's disease is a neurodegenerative illness that causes neuronal death most extensively within the basal ganglia. There is a broad class of neurologic disorders associated with the expansion of polyglutamine (polyQ) repeats in numerous proteins. Several other molecular mechanisms have also been implicated in HD pathology, including brain-derived neurotrophic factor (BDNF), mitochondrial dysfunction, and altered synaptic plasticity in central spiny neurons. HD pathogenesis and the effectiveness of therapy approaches have been better understood through the use of animal models. The pathological manifestations of the disease were reproduced by early models of glutamate analog toxicity and mitochondrial respiration inhibition. Because the treatments available for HD are quite limited, it is important to have a definite preclinical model that mimics all the aspects of the disease. It can be used to study mechanisms and validate candidate therapies. Although there hasn't been much success in translating animal research into clinical practice, each model has something special to offer in the quest for a deeper comprehension of HD's neurobehavioral foundations. This review provides insight into various in-vitro-and in-vivo models of HD which may be useful in the screening of newer therapeutics for this incapacitating disorder.
亨廷顿病是一种神经退行性疾病,导致基底神经节中神经元死亡最为广泛。有一大类与许多蛋白质中聚谷氨酰胺(polyQ)重复扩展相关的神经紊乱。其他几个分子机制也与 HD 病理学有关,包括脑源性神经营养因子(BDNF)、线粒体功能障碍和中枢棘神经元的突触可塑性改变。通过使用动物模型,更好地理解了 HD 的发病机制和治疗方法的有效性。疾病的病理表现通过早期的谷氨酸类似物毒性和线粒体呼吸抑制模型得到了重现。由于 HD 的治疗方法非常有限,因此拥有一个能够模拟疾病所有方面的明确的临床前模型非常重要。它可以用于研究机制并验证候选疗法。尽管将动物研究转化为临床实践并没有取得太大的成功,但每个模型在探索 HD 的神经行为基础方面都有一些特别的贡献。本文综述了各种体外和体内的 HD 模型,这些模型可能有助于筛选针对这种使人丧失能力的疾病的新疗法。