热休克蛋白家族 B（小）成员 8 (HSPB8) 是一种 22 kDa 普遍表达的蛋白质，属于小热休克蛋白家族。 HSPB8 参与各种细胞机制，主要与蛋白毒性应激反应相关，以及炎症、细胞分裂和迁移等其他过程。 HSPB8 结合错误折叠的客户，通过分子伴侣辅助的选择性自噬协助蛋白质重折叠或降解，从而防止其聚集。与此功能一致，HSPB8 的促降解活性在多种以蛋白质错误折叠和聚集为特征的神经退行性和神经肌肉疾病中具有保护作用。在癌症中，HSPB8 具有双重作用，能够发挥促肿瘤或抗肿瘤活性，具体取决于所研究的癌症模型表达的途径和因子。此外，HSPB8通过调节炎症反应在不同疾病中发挥保护功能，这不仅是神经退行性疾病的特征，也是影响神经系统的其他慢性或急性疾病的特征，例如多发性硬化症和小脑出血。值得注意的是，HSPB8 调节可能代表了其他神经系统疾病的一种治疗方法，这些疾病是其他疾病的继发后果。这是与糖尿病相关的认知障碍的例子，其中HSPB8通过确保线粒体稳态发挥保护活性。本综述旨在总结HSPB8在不同病理条件下的多样化和多种功能，重点关注其调节的有益作用。将讨论针对 HSPB8 及其调控途径的基于药物和替代治疗方法，强调细胞和组织特异性递送的新策略如何代表疾病治疗进展的途径。版权所有 © 2025 版权所有：© 2025 神经再生研究。

Heat shock protein family B (small) member 8 (HSPB8) is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins. HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation, cell division, and migration. HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy. In line with this function, the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation. In cancer, HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation. Moreover, HSPB8 exerts a protective function in different diseases by modulating the inflammatory response, which characterizes not only neurodegenerative diseases, but also other chronic or acute conditions affecting the nervous system, such as multiple sclerosis and intracerebellar hemorrhage. Of note, HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases. This is the case of cognitive impairment related to diabetes mellitus, in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions, focusing on the beneficial effects of its modulation. Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed, emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.