Department of Anatomy, Dongguk University College of Medicine, Gyeongju, 38066, Republic of Korea.
Department of Pharmacy, Faculty of Life and Earth Sciences, Jagannath University, Dhaka, 1100, Bangladesh.
Neurochem Int. 2021 May;145:105011. doi: 10.1016/j.neuint.2021.105011. Epub 2021 Mar 10.
Defective proteostasis is associated with the gradual accumulations of misfolded proteins and is a hallmark of many age-associated neurodegenerative diseases. In the aged brain, maintenance of the proteostasis network presents a substantial challenge, and its loss contributes to the onset and progression of neurological diseases associated with cognitive decline due to the generation of toxic protein aggregates, a process termed 'proteinopathy'. Emerging evidence suggests that reversing proteinopathies by boosting proteostasis might provide an effective means of preventing neurodegeneration. From this perspective, phytochemicals may play significant roles as potent modulators of the proteostasis network, as previous reports have suggested they can interact with various network components to modify pathologies and confer neuroprotection. This review focuses on some potent phytochemicals that directly or indirectly modulate the proteostasis network and on their possible molecular targets. In addition, we propose strategies for the natural product-based modulation of proteostasis machinery that target proteinopathies.
蛋白质稳态失调与错误折叠蛋白的逐渐积累有关，是许多与年龄相关的神经退行性疾病的标志。在衰老的大脑中，维持蛋白质稳态网络是一个巨大的挑战，其丧失导致与认知能力下降相关的神经疾病的发生和进展，这一过程被称为“蛋白质病”。新出现的证据表明，通过提高蛋白质稳态来逆转蛋白质病可能是预防神经退行性变的有效方法。从这个角度来看，植物化学物质可能作为蛋白质稳态网络的有效调节剂发挥重要作用，因为之前的报告表明它们可以与各种网络成分相互作用，以改变病理学并提供神经保护。本综述重点介绍了一些直接或间接调节蛋白质稳态网络的有效植物化学物质及其可能的分子靶点。此外，我们还提出了基于天然产物调节蛋白质稳态机制以靶向蛋白质病的策略。
