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的细胞实体，是正常健康和有机体生存所必需的。蛋白质组是细胞表达蛋白质的绝对集合，可调节与生命各个领域相关的多种生理功能。在衰老的细胞中或在不利的细胞条件下，蛋白质错误折叠会产生与神经退行性疾病和衰老有关的常见病理事件。蛋白质组学研究的最新进展在我们的知识上系统地产生了一些进展，即蛋白质的错误折叠或它们的积累如何导致蛋白质组功能的损伤或耗竭。仍然，这种无法恢复的损失的根本原因尚不清楚，这种未解决的过渡如何导致神经退行性病变的多因素挑战性退行性病理状况。在这篇评论中，我们特别关注并系统地总结了维持蛋白稳态的各种分子机制，并讨论了不断发展的神经生物学策略，有前途的天然药物和药理学候选物，这些药物可用于解决蛋白病的问题。本文强调了一个紧迫的需求，对于我们来说，认识蛋白质变形的基本原理以设计新的分子框架和卓有成效的策略来揭示蛋白质组缺陷与衰老和神经退行性疾病的关系非常重要。对蛋白质组学和神经生物学挑战的进展联系的加深理解可能会在不久的将来提供新的基本概念，这些新概念是基于与受损蛋白变性和神经退行性疾病有关的药理学基础的。