Dysregulation of Heat Shock Proteins in Neurodegenerative Diseases: Restorative Roles of Small Molecules and Natural Compounds
Dysregulation of Heat Shock Proteins in Neurodegenerative Diseases: Restorative Roles of Small Molecules and Natural Compounds
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DOI：
10.1007/978-3-030-24285-5_7
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
P. Maiti;J. Manna
中科院分区：
文献类型：
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作者：
P. Maiti;J. Manna
错误折叠的淀粉样蛋白的逐渐沉积在许多神经退行性疾病的发病、进展和严重程度中发挥着重要作用。细胞中存在几种参与这些蛋白质降解的蛋白质清除机制。因此，这些系统被认为是细胞蛋白质稳态的关键参与者。分子伴侣，例如热休克蛋白（HSP）就是其中之一，它在这些错误折叠的蛋白质聚集体的降解中发挥着至关重要的作用。事实上，较大的蛋白质聚集体通过吞噬作用或巨自噬机制被降解，而较小的蛋白质聚集体则在 HSP 的帮助下或通过泛素蛋白酶体系统在溶酶体内降解。重要的是，热休克蛋白在不同的神经退行性疾病中变得失调。因此，增强细胞蛋白质质量控制机制，特别是分子伴侣的水平和活性，可以抑制错误折叠的蛋白质聚集并恢复细胞功能。几种小分子和天然多酚已被证明可以在不同的神经退行性疾病中维持 HSP 水平。在本书章节中，我们讨论了目前对热休克蛋白在蛋白质错误折叠神经系统疾病中的作用的理解，特别是在阿尔茨海默病、帕金森病、亨廷顿病、朊病毒病和 tau 蛋白病中。此外，我们还强调了天然多酚对 HSP 的调节作用，作为蛋白质错误折叠神经系统疾病的治疗策略。
Gradual depositions of misfolded amyloid proteins play major roles in onset, progression and severity of many neurodegenerative diseases. Several protein clearance machineries exist in the cell which are involved in degradation of these proteins. Therefore, these systems are considered the key players of cellular protein homeostasis. A molecular chaperone, such as heat shock protein (HSP) is one of them, which play a crucial role in degradation of these misfolded protein aggregates. Indeed, larger protein aggregates are degraded by phagocytosis or macroautophagy mechanism, whereas smaller protein aggregates are degraded within the lysosomes with the help of HSP or via ubiquitin proteosomal system. Importantly, the HSPs become dysregulated in different neurodegenerative diseases. Therefore, enhancement of cellular protein quality control machineries, specifically the levels and activities of molecular chaperones could suppress the misfolded protein aggregation and can restore cellular function. Several small molecules and natural polyphenols have been shown to maintain HSP levels in different neurodegenerative diseases. In this book chapter, we discuss the current understanding of the roles of HSPs in protein misfolding neurological diseases, especially on Alzheimer’s, Parkinson’s, Huntington’s, prion diseases and tauopathies. In addition, we also highlighted the modulatory roles of natural polyphenols on HSPs as a therapeutic strategy for protein misfolding neurological diseases.