Bhat Sheraz Ahmad, Kamal Mohammad Amjad, Yarla Nagendra Sastry, Ashraf Ghulam Md
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Curr Top Med Chem. 2017;17(12):1371-1378. doi: 10.2174/1568026616666161222121229.
The maintenance of health requires successful cell functioning, which in turn depends upon the proper and active conformation of proteins besides other biomolecules. However, occasionally these proteins may misfold and lead to the appearance and progression of protein conformational diseases. These diseases apart from others include several neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and other lesser known diseases. Although much knowledge has been gained, these NDDs still warrant advance research in the elucidation of their mechanisms as well as effective therapeutic interventions and proper management. There is an ever-growing and urgent need to improve the diagnosis and management of NDDs due to their devastating nature, serious social impact and neuropsychiatric symptoms. It is also envisioned that we may be able to encourage, develop, and strengthen the cell defenses against amyloid toxicity and prevent neuronal destruction and consequently neurodegeneration. In this review, the implications of protein misfolding and aggregation in NDDs are discussed along with some of the most recent findings on the curative and beneficial effects of natural molecules such as polyphenols. This paper also reviews the anti-aggregation and protective effects of some organic and peptidic compounds duly supported experimentally, as prospective future therapeutics for NDDs. The synopses presented in this review shall prove helpful in further understanding of the causes, cures and management of lethal NDDs.
维持健康需要细胞正常运作,而这又依赖于蛋白质以及其他生物分子的正确且活跃的构象。然而,这些蛋白质偶尔可能会错误折叠,导致蛋白质构象疾病的出现和发展。除其他疾病外,这些疾病还包括几种神经退行性疾病(NDDs),如阿尔茨海默病、帕金森病、亨廷顿舞蹈症、多发性硬化症、肌萎缩侧索硬化症以及其他一些不太知名的疾病。尽管已经取得了很多知识,但这些神经退行性疾病在阐明其发病机制以及有效的治疗干预和合理管理方面仍需要进一步研究。由于神经退行性疾病具有毁灭性本质、严重的社会影响和神经精神症状,因此对其诊断和管理的改进需求日益迫切且十分必要。人们还设想,我们或许能够鼓励、发展并增强细胞对淀粉样毒性的防御能力,防止神经元破坏,进而预防神经退行性变。在这篇综述中,我们将讨论蛋白质错误折叠和聚集在神经退行性疾病中的影响,以及一些关于天然分子(如多酚)的治疗和有益作用的最新研究结果。本文还综述了一些有机化合物和肽类化合物的抗聚集和保护作用,这些作用已得到实验充分支持,有望成为未来治疗神经退行性疾病的药物。本综述中的内容将有助于进一步理解致命性神经退行性疾病的病因、治疗方法和管理措施。