当前位置: X-MOL 学术Neurochem. Int. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The small heat shock proteins, especially HspB4 and HspB5 are promising protectants in neurodegenerative diseases
Neurochemistry international ( IF 4.2 ) Pub Date : 2018-02-07 , DOI: 10.1016/j.neuint.2018.02.006
Zhihui Zhu , Georg Reiser

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.



中文翻译:

较小的热激蛋白,尤其是HspB4和HspB5是神经退行性疾病中有希望的保护剂

小型热激蛋白(sHsps)是分子量在12至43 kDa之间的一组蛋白质。目前,该家族的11个成员已被分类,即HspB1至HspB11。已观察到在脑中表达的HspB1,HspB2,HspB5,HspB6,HspB7和HspB8与神经退行性疾病的病理相关,包括帕金森氏症,阿尔茨海默氏病,亚历山大氏病,多发性硬化症以及与人类免疫缺陷病毒相关的痴呆症。具体来说,sHsps与错误折叠和破坏性蛋白质聚集体相互作用,例如AxD中的胶质纤维酸性蛋白,阿尔茨海默氏病中的β-淀粉样肽聚集体,肌萎缩性侧索硬化症中的超氧化物歧化酶1以及亨廷顿的胞嘧啶-腺嘌呤-鸟嘌呤/聚谷氨酰胺(CAG / PolyQ)疾病,脊髓小脑共济失调3型,脊髓球型肌萎缩症,以减少毒性或增加这些蛋白质聚集体的清除率。HspB4在大脑中的表达程度仍存在争议。对于神经保护机制,sHsps可减轻线粒体功能障碍,减少错折叠蛋白的积累,阻断氧化/亚硝化应激,并使神经元凋亡和神经炎症最小化,这是反映神经退行性疾病进展和发展的分子机制。神经退行性疾病的发病率增加,增加了寻找有效方法以最小程度的副作用挽救神经组织免于变性的搜索。已经发现sHsps发挥神经保护功能。HspB5已被强调可减轻实验性自身免疫性脑脊髓炎的小鼠模型的瘫痪,为该疾病提供治疗基础。在这篇综述中,我们讨论了sHsps在神经系统中精心设计的特性和保护机制的当前理解,突出了sHsps在神经退行性疾病中的有希望的治疗作用。

更新日期:2018-02-07
down
wechat
bug