Pathophysiological role of high mobility group box-1 signaling in neurodegenerative diseases.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2024-11-15 DOI:10.1007/s10787-024-01595-9

Vishal Kumar, Puneet Kumar

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引用次数: 0

Abstract

Nucleocytoplasmic translocation of HMGB1 (high mobility group box-1) plays a significant role in disease progression. Several methods contribute to the translocation of HMGB1 from the nucleus to the cytoplasm, including inflammasome activation, TNF-α signaling, CRM1-mediated transport, reactive oxygen species (ROS), JAK/STAT pathway, RIP3-mediated p53 involvement, XPO-1-mediated transport, and calcium-dependent mechanisms. Due to its diverse functions at various subcellular locations, HMGB1 has been identified as a crucial factor in several Central Nervous System (CNS) disorders, including Huntington's disease (HD), Parkinson's disease (PD), and Alzheimer's disease (AD). HMGB1 displays a wide array of roles in the extracellular environment as it interacts with several receptors, including CXCR4, TLR2, TLR4, TLR8, and RAGE, by engaging in these connections, HMGB1 can effectively regulate subsequent signaling pathways, hence exerting an impact on the progression of brain disorders through neuroinflammation. Therefore, focusing on treating neuroinflammation could offer a common therapeutic strategy for several disorders. The objective of the current literature is to demonstrate the pathological role of HMGB1 in various neurological disorders. This review also offers insights into numerous therapeutic targets that promise to advance multiple treatments intended to alleviate brain illnesses.

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高迁移率基团盒-1 信号在神经退行性疾病中的病理生理学作用

HMGB1（高迁移率基团盒-1）的核胞浆转位在疾病进展中起着重要作用。有几种方法可促使 HMGB1 从细胞核转位到细胞质，包括炎性体激活、TNF-α 信号传导、CRM1 介导的转运、活性氧（ROS）、JAK/STAT 途径、RIP3 介导的 p53 参与、XPO-1 介导的转运以及钙依赖机制。由于 HMGB1 在不同亚细胞位置具有多种功能，它已被确定为几种中枢神经系统（CNS）疾病的关键因素，包括亨廷顿氏病（HD）、帕金森氏病（PD）和阿尔茨海默病（AD）。HMGB1 在细胞外环境中发挥着广泛的作用，它与多种受体（包括 CXCR4、TLR2、TLR4、TLR8 和 RAGE）相互作用，通过这些连接，HMGB1 可以有效调节后续信号通路，从而通过神经炎症对脑部疾病的进展产生影响。因此，关注神经炎症的治疗可以为多种疾病提供一种共同的治疗策略。目前的文献旨在证明 HMGB1 在各种神经系统疾病中的病理作用。本综述还提供了对众多治疗靶点的见解，这些靶点有望推动旨在缓解脑部疾病的多种治疗方法。

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 [...]