Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, 342011, India.
Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon, 122051, India.
Prog Neurobiol. 2017 Dec;159:1-38. doi: 10.1016/j.pneurobio.2017.08.005. Epub 2017 Sep 1.
Proteins are ordered useful cellular entities, required for normal health and organism's survival. The proteome is the absolute set of cellular expressed proteins, which regulates a wide range of physiological functions linked with all domains of life. In aging cells or under unfavorable cellular conditions, misfolding of proteins generates common pathological events linked with neurodegenerative diseases and aging. Current advances of proteome studies systematically generates some progress in our knowledge that how misfolding of proteins or their accumulation can contribute to the impairment or depletion of proteome functions. Still, the underlying causes of this unrecoverable loss are not clear that how such unsolved transitions give rise to multifactorial challengeable degenerative pathological conditions in neurodegeneration. In this review, we specifically focus and systematically summarize various molecular mechanisms of proteostasis maintenance, as well as discuss progressing neurobiological strategies, promising natural and pharmacological candidates, which can be useful to counteract the problem of proteopathies. Our article emphasizes an urgent need that now it is important for us to recognize the fundamentals of proteostasis to design a new molecular framework and fruitful strategies to uncover how the proteome defects are associated with aging and neurodegenerative diseases. A enhance understanding of progress link with proteome and neurobiological challenges may provide new basic concepts in the near future, based on pharmacological agents, linked with impaired proteostasis and neurodegenerative diseases.
蛋白质是有序的有用细胞实体,是维持正常健康和生物生存所必需的。蛋白质组是细胞表达蛋白质的绝对集合,它调节着与生命所有领域相关的广泛的生理功能。在衰老细胞或不利的细胞条件下,蛋白质错误折叠会产生与神经退行性疾病和衰老相关的常见病理事件。目前蛋白质组研究的进展系统地使我们的知识取得了一些进展,即蛋白质的错误折叠或积累如何导致蛋白质组功能的损伤或耗竭。尽管如此,这种不可恢复的损失的根本原因尚不清楚,这些未解决的转变如何导致神经退行性变中多因素挑战性退行性病理状况。在这篇综述中,我们特别关注并系统地总结了维持蛋白质稳态的各种分子机制,并讨论了正在进展的神经生物学策略、有前途的天然和药理学候选物,这些策略可能有助于对抗蛋白质病的问题。我们的文章强调了一个紧迫的需求,即现在我们有必要认识到蛋白质稳态的基础,以设计一个新的分子框架和富有成效的策略,揭示蛋白质组缺陷与衰老和神经退行性疾病的关联。对与蛋白质组和神经生物学挑战相关的进展的深入了解,可能会在不久的将来基于与蛋白质稳态受损和神经退行性疾病相关的药理学药物,提供新的基本概念。