用于治疗亨廷顿疾病的天然生物活性化合物的药理学:概述

Dipak Dilipkumar Gadade , Rashmi Sareen , Nitin Jain , Kamal Shah , Vimal Kumar , Anuj Modi , Nagendra Singh Chauhan
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摘要

亨廷顿氏病(HtD)是一种遗传性神经退行性疾病,对全球老年人群构成威胁。亨廷顿舞蹈症是由于亨廷顿舞蹈症基因中的胞嘧啶-腺嘌呤-鸟嘌呤(CAG)重复,进而形成突变亨廷顿蛋白(mHtt),导致神经元功能障碍和细胞死亡。亨廷顿舞蹈症的症状通常在成年后开始出现,进展缓慢,会导致精神障碍、运动障碍和认知功能障碍。HtD主要影响纹状体和皮层的中棘神经元。为了阐明导致神经元功能障碍和细胞死亡的潜在机制,人们提出了多种假说。这通常包括分子遗传学、氧化应激(OS)、兴奋毒性、线粒体损伤等。天然生物活性物质是从植物、动物和微生物中提取的各种化合物。研究发现,天然生物活性物质可调节参与 HtD 发病的多种信号通路,并具有减少 OS、神经炎症和神经元死亡的潜力,而这些正是 HtD 的关键病理过程。大多数天然生物活性物质通过下调OS、兴奋毒性、线粒体功能障碍、小胶质细胞失活、神经炎症和/或上调泛素蛋白酶体系统、自噬&;溶酶体降解途径、细胞凋亡途径、嘌呤能信号途径来提供保护。此外,我们还讨论了开发基于天然生物活性成分的安全有效的 HtD 治疗方法所面临的机遇和挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacology of natural bioactive compounds used for management of Huntington diseases: An overview
Huntington's disease (HtD), an inherited genetic neurodegenerative disorder, posed threat to elderly population world-wide. HtD is caused by the repetition of cytosine-adenine-guanine (CAG) in HtD gene, which further leads to the formation of a mutant Huntington (mHtt) protein that is responsible for neuronal dysfunction and cell death. Symptoms of HtD usually begin in adulthood and progress slowly, resulting in psychiatric disturbances, motor deficits and cognitive dysfunction. The medium spiny neurons of the striatum and cortex are mainly affected in HtD. Multiple hypotheses have been proposed to elucidate the underlying mechanisms that lead to neuronal dysfunction and cell death. This typically includes molecular genetics, oxidative stress (OS), excitotoxicity, mitochondrial impairment etc. Natural bioactives are a diverse group of compounds derived from plants, animals and microorganisms. They have been found to modulate multiple signaling pathways involved in the development of HtD and have potentials in reducing OS, neuroinflammation, and neuronal death, which are key pathological processes in HtD.Mostly natural bioactive offers protection either by down-regulating the OS, excitotoxicity, mitochondrial dysfunctions, microglial inactivation, neuroinflammation and/or by upregulating ubiquitin-proteasome system, autophagy & lysosomal degradation pathway, apoptotic pathway, purinergic signaling pathway.In this chapter, we have summarized various natural bioactives that exhibit therapeutic potential against HtD. Furthermore, we have discussed the opportunities and challenges associated with the development of safe and effective natural bioactives-based therapies against HtD.
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