Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India.
School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, India.
Cell Physiol Biochem. 2021 Mar 27;55(S2):49-70. doi: 10.33594/000000350.
Major cause of proteopathies is the accumulation of unwanted mutant and aberrant proteins. We know that imperfect ageing is one of chief risk factor for most neurodegenerative diseases. Neurodegenerative diseases are characterized by mutant misfolded protein aggregates developing neural stress and debilitating several neuronal processes. Reducing the levels of these abnormal proteins using various natural compounds can be a promising possible therapeutic strategy. But the advancement of natural compound-based therapies in neurodegeneration and imperfect ageing treatment has been impeded by different challenges and unknown molecular patho-mechansim. The complexity in the causative factors generating protein aggregates in neurons and their respective path towards cell death is high, making it a difficult to treat disorder. Several plant based compounds have proven to promote different neuronal homeostasis mechanisms. However, there is a pressing necessity to screen, find and develop cost-effective natural compound-based new therapeutic interventions which can be useful for clinical purposes in treating neurodegenerative ailments. It is critical to discuss and elaborate the applications of few important natural compounds and their connections with following mechanisms: protein disposal machineries, apoptosis, neuroinflammation, neuronal development, synaptogenesis and neural homeostasis. This article summarizes the current knowledge and discusses the unanswered questions linked with the natural compounds and their promising therapeutic avenues primarily focusing on neurodegenerative diseases and defective neurobiological mechanisms.
蛋白病的主要病因是异常和突变蛋白的积累。我们知道,不完善的衰老过程是大多数神经退行性疾病的主要风险因素之一。神经退行性疾病的特征是突变错误折叠的蛋白质聚集体引发神经应激,削弱多种神经元过程。使用各种天然化合物降低这些异常蛋白的水平可能是一种很有前途的治疗策略。但由于存在不同的挑战和未知的分子病理机制,基于天然化合物的疗法在神经退行性变和衰老治疗方面的进展受到了阻碍。在神经元中产生蛋白质聚集体的致病因素以及它们各自的细胞死亡途径非常复杂,使得这种疾病难以治疗。一些植物来源的化合物已被证明能促进不同的神经元稳态机制。然而,迫切需要筛选、发现和开发具有成本效益的基于天然化合物的新治疗干预措施,这些措施可用于治疗神经退行性疾病的临床目的。讨论和阐述几种重要的天然化合物及其与以下机制的联系非常重要:蛋白处理机制、细胞凋亡、神经炎症、神经元发育、突触发生和神经稳态。本文总结了目前的知识,并讨论了与天然化合物及其有前途的治疗途径相关的未解决问题,主要侧重于神经退行性疾病和神经生物学缺陷机制。