Institut für Inflammation und Neurodegeneration (Neurobiochemie), Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, 39120 Magdeburg, Germany; College of Medicine, Department of Physiology, University of Kentucky, Lexington, KY, USA.
Institut für Inflammation und Neurodegeneration (Neurobiochemie), Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, 39120 Magdeburg, Germany.
Neurochem Int. 2018 May;115:69-79. doi: 10.1016/j.neuint.2018.02.006. Epub 2018 Feb 7.
Small heat shock proteins (sHsps) are a group of proteins with molecular mass between 12 and 43 kDa. Currently, 11 members of this family have been classified, namely HspB1 to HspB11. HspB1, HspB2, HspB5, HspB6, HspB7, and HspB8, which are expressed in brain have been observed to be related to the pathology of neurodegenerative diseases, including Parkinson's, Alzheimer's, Alexander's disease, multiple sclerosis, and human immunodeficiency virus-associated dementia. Specifically, sHsps interact with misfolding and damaging protein aggregates, like Glial fibrillary acidic protein in AxD, β-amyloid peptides aggregates in Alzheimer's disease, Superoxide dismutase 1 in Amyotrophic lateral sclerosis and cytosine-adenine-guanine/polyglutamine (CAG/PolyQ) in Huntington's disease, Spinocerebellar ataxia type 3, Spinal-bulbar muscular atrophy, to reduce the toxicity or increase the clearance of these protein aggregates. The degree of HspB4 expression in brain is still debated. For neuroprotective mechanisms, sHsps attenuate mitochondrial dysfunctions, reduce accumulation of misfolded proteins, block oxidative/nitrosative stress, and minimize neuronal apoptosis and neuroinflammation, which are molecular mechanisms commonly accepted to mirror the progression and development of neurodegenerative diseases. The increasing incidence of the neurodegenerative diseases enhanced search for effective approaches to rescue neural tissue from degeneration with minimal side effects. sHsps have been found to exert neuroprotective functions. HspB5 has been emphasized to reduce the paralysis in a mouse model of experimental autoimmune encephalomyelitis, providing a therapeutic basis for the disease. In this review, we discuss the current understanding of the properties and the mechanisms of protection orchestrated by sHsps in the nervous system, highlighting the promising therapeutic role of sHsps in neurodegenerative diseases.
小分子热休克蛋白（sHsps）是一组分子量在 12 至 43 kDa 之间的蛋白质。目前，该家族已分类出 11 个成员，即 HspB1 至 HspB11。在大脑中表达的 HspB1、HspB2、HspB5、HspB6、HspB7 和 HspB8 与神经退行性疾病的病理学有关，包括帕金森病、阿尔茨海默病、亚历山大病、多发性硬化症和人类免疫缺陷病毒相关痴呆症。具体而言，sHsps 与错误折叠和损伤的蛋白质聚集体相互作用，如 AxD 中的神经胶质纤维酸性蛋白、阿尔茨海默病中的 β-淀粉样肽聚集体、肌萎缩侧索硬化症中的超氧化物歧化酶 1 和亨廷顿病中的胞嘧啶-腺嘌呤-鸟嘌呤/多聚谷氨酰胺（CAG/PolyQ）、脊髓小脑共济失调 3 型、脊髓延髓肌萎缩症，以降低这些蛋白质聚集体的毒性或增加其清除率。大脑中 HspB4 的表达程度仍存在争议。对于神经保护机制，sHsps 减轻线粒体功能障碍，减少错误折叠蛋白质的积累，阻断氧化/硝化应激，最大限度地减少神经元凋亡和神经炎症，这些分子机制通常被认为反映了神经退行性疾病的进展和发展。神经退行性疾病的发病率不断增加，促使人们寻找有效的方法来保护神经组织免受退化，同时尽量减少副作用。已经发现 sHsps 具有神经保护功能。HspB5 已被强调可减少实验性自身免疫性脑脊髓炎小鼠模型中的瘫痪，为该疾病提供了治疗基础。在本综述中，我们讨论了 sHsps 在神经系统中的特性和保护机制的最新理解，强调了 sHsps 在神经退行性疾病中的有前途的治疗作用。
