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S100B 蛋白在神经和非神经疾病中的治疗作用日益凸显。

Growing role of S100B protein as a putative therapeutic target for neurological- and nonneurological-disorders.

机构信息

Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy; IRCCS San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, 20132 Milan, Italy.

Department of Translational Medicine and Surgery, Section of General Pathology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 1-8, 00168 Rome, Italy.

出版信息

Neurosci Biobehav Rev. 2021 Aug;127:446-458. doi: 10.1016/j.neubiorev.2021.04.035. Epub 2021 May 7.

DOI:10.1016/j.neubiorev.2021.04.035
PMID:33971224
Abstract

S100B is a calcium-binding protein mainly expressed by astrocytes, but also localized in other definite neural and extra-neural cell types. While its presence in biological fluids is widely recognized as a reliable biomarker of active injury, growing evidence now indicates that high levels of S100B are suggestive of pathogenic processes in different neural, but also extra-neural, disorders. Indeed, modulation of S100B levels correlates with the occurrence of clinical and/or toxic parameters in experimental models of diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, muscular dystrophy, multiple sclerosis, acute neural injury, inflammatory bowel disease, uveal and retinal disorders, obesity, diabetes and cancer, thus directly linking the levels of S100B to pathogenic mechanisms. In general, deletion/inactivation of the protein causes the improvement of the disease, whereas its over-expression/administration induces a worse clinical presentation. This scenario reasonably proposes S100B as a common therapeutic target for several different disorders, also offering new clues to individuate possible unexpected connections among these diseases.

摘要

S100B 是一种钙结合蛋白,主要由星形胶质细胞表达,但也定位于其他明确的神经和神经外细胞类型中。虽然其在生物液中的存在被广泛认为是活跃损伤的可靠生物标志物,但越来越多的证据表明,S100B 的高水平提示不同的神经,甚至神经外,疾病中的致病过程。事实上,在阿尔茨海默病和帕金森病、肌萎缩侧索硬化症、肌肉营养不良症、多发性硬化症、急性神经损伤、炎症性肠病、葡萄膜和视网膜疾病、肥胖症、糖尿病和癌症等疾病的实验模型中,S100B 水平的调节与临床和/或毒性参数的发生相关,从而将 S100B 水平直接与致病机制联系起来。一般来说,该蛋白的缺失/失活会改善疾病,而其过度表达/给药会导致更严重的临床症状。这种情况合理地将 S100B 作为几种不同疾病的共同治疗靶点,也为这些疾病之间可能存在的意外联系提供了新的线索。

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