{"title":"Diverse role of S100 calcium-binding protein B in alzheimer's disease: pathological mechanisms and therapeutic implications.","authors":"Sampriti Sarkar, Pratyush Porel, Sourabh Kosey, Khadga Raj Aran","doi":"10.1007/s10787-025-01697-y","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10787-025-01697-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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 [...]