Diverse role of S100 calcium-binding protein B in alzheimer's disease: pathological mechanisms and therapeutic implications.

IF 4.6 2区 医学 Q2 IMMUNOLOGY
Inflammopharmacology Pub Date : 2025-04-01 Epub Date: 2025-03-09 DOI:10.1007/s10787-025-01697-y
Sampriti Sarkar, Pratyush Porel, Sourabh Kosey, Khadga Raj Aran
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引用次数: 0

Abstract

S100 calcium-binding protein B, a member of the S100 protein family, plays an important role in the pathogenesis of Alzheimer's disease. Alzheimer's disease, a neurodegenerative disorder, is characterized by amyloid-beta plaques, neurofibrillary tangles, progressive dementia, and severe neuroinflammation. S100 calcium-binding protein B, predominantly secreted by astrocytes, exhibits a dual role in Alzheimer's disease, where at low (nanomolar) concentrations, it exhibits neurotrophic and neuroprotective effects and enhances synaptic plasticity, while at higher concentrations, it contributes to neuroinflammation and neuronal damage. In addition to its pathological roles in Alzheimer's disease, S100 calcium-binding protein B is also considered a potential biomarker, as increased levels correlate with cognitive decline and disease progression in cerebrospinal fluid. Targeting S100 calcium-binding protein B and/or its interaction with the receptor for advanced glycation end-products seems to be a potential target for therapeutic intervention. The development of multiple treatment approaches, such as pharmacological inhibitors, immunotherapy, and modulation of S100 calcium-binding protein B / receptor for advanced glycation end-products signalling pathways, might help to reduce neuroinflammation and amyloid-beta deposition effectively. This review aims to provide an overview of the role of S100 calcium-binding protein B in Alzheimer's disease and to explore its potential as a treatment target, well-grounded in its dual nature. Understanding S100 calcium-binding protein B's involvement in the pathogenesis of Alzheimer's disease may advance its application as a biomarker and help in the development of new treatment strategies, ultimately improving patients' quality of life.

S100钙结合蛋白B在阿尔茨海默病中的多种作用:病理机制和治疗意义
S100钙结合蛋白B是S100蛋白家族的成员,在阿尔茨海默病的发病机制中起重要作用。阿尔茨海默病是一种神经退行性疾病,其特征是淀粉样斑块、神经原纤维缠结、进行性痴呆和严重的神经炎症。S100钙结合蛋白B主要由星形胶质细胞分泌,在阿尔茨海默病中表现出双重作用,在低(纳摩尔)浓度下,它表现出神经营养和神经保护作用,增强突触可塑性,而在较高浓度下,它有助于神经炎症和神经元损伤。除了在阿尔茨海默病中的病理作用外,S100钙结合蛋白B也被认为是一种潜在的生物标志物,因为脑脊液中S100钙结合蛋白B水平升高与认知能力下降和疾病进展相关。靶向S100钙结合蛋白B和/或其与晚期糖基化终产物受体的相互作用似乎是治疗干预的潜在目标。多种治疗方法的发展,如药物抑制剂、免疫疗法和S100钙结合蛋白B /受体对晚期糖基化终产物信号通路的调节,可能有助于有效减少神经炎症和淀粉样蛋白沉积。本综述旨在概述S100钙结合蛋白B在阿尔茨海默病中的作用,并探讨其作为治疗靶点的潜力,充分基于其双重性质。了解S100钙结合蛋白B在阿尔茨海默病发病机制中的作用可能会促进其作为生物标志物的应用,并有助于开发新的治疗策略,最终改善患者的生活质量。
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来源期刊
Inflammopharmacology
Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY
CiteScore
8.00
自引率
3.40%
发文量
200
期刊介绍: Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]
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