Impact of corticoid receptors on Alzheimer's disease: a neuroendocrine perspective.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-05-01 Epub Date: 2025-04-18 DOI:10.1007/s10787-025-01734-w

Falguni Goel, Daksh Kumar, Anushka Sharma

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引用次数: 0

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has been strongly associated with changes in corticoid receptor function and HPA axis dysregulation. This review gives an overview of the complex role of GC and MC receptors in AD, especially how chronic exposure to elevated cortisol contributes to hippocampal degeneration, oxidative stress, and cognitive decline. Specific emphasis lies with cortisol, brought to the attention of neurotoxicity, and relates it to Cushing syndrome with chronic hyper-cortisolism simulating cognitive and structural impairments seen in AD. The impact of HPA axis over-activity in AD pathology is presented, demonstrating its contribution to neuro-inflammation and possible utilization as a biomarker for disease progression. This review further includes pharmacological strategies that modulate corticoid receptors for the reduction of GC-induced neurotoxicity and includes selective GR antagonists and MR agonists. Lifestyle modifications, which modulate HPA activity, are the other non-pharmacological approach to managing AD. Finally, novel drugs and interventions targeting the regulation of GC, anti-inflammatory pathways, as well as attenuation of oxidative stress are emerging strategies. Such a strategy implies that it is possible that receptor activity balance can delay or arrest AD progression.

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皮质激素受体对阿尔茨海默病的影响：神经内分泌的观点。

阿尔茨海默病（AD）是一种进行性神经退行性疾病，与皮质激素受体功能改变和HPA轴失调密切相关。本文综述了GC和MC受体在AD中的复杂作用，特别是长期暴露于皮质醇升高如何导致海马变性、氧化应激和认知能力下降。特别强调的是皮质醇，引起了神经毒性的注意，并将其与库欣综合征（Cushing syndrome）与慢性高皮质醇血症（chronic hypercorsolism）联系起来，这种疾病模拟了AD中出现的认知和结构损伤。HPA轴过度活动在AD病理中的影响，证明了它对神经炎症的贡献，并可能作为疾病进展的生物标志物。本综述进一步包括调节皮质激素受体以减少gc诱导的神经毒性的药理学策略，包括选择性GR拮抗剂和MR激动剂。改变生活方式可以调节HPA的活性，这是治疗AD的另一种非药物方法。最后，针对GC调节、抗炎途径以及氧化应激衰减的新型药物和干预措施正在出现。这样的策略意味着受体活性平衡可能延缓或阻止AD的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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 [...]