CAMK2G in subcellular Ca2+ homeostasis: Molecular mechanisms and therapeutic targeting

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-09-13 DOI:10.1016/j.bcp.2025.117323

Yashi Cao , Zengyue Pan , Xiner Shen , Zhifei Xu , Xiaochun Yang , Bo Yang , Peihua Luo , Hao Yan , Qiaojun He

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引用次数: 0

Abstract

The Ca²⁺/calmodulin-dependent protein kinase II (CAMK2) family, consisting of subtypes A, B, D, and G, plays a pivotal role in decoding Ca²⁺ signals, an essential process in cellular communication and function. Among these, CAMK2G is notably widespread across various body tissues, with predominant expression in neurons and cardiomyocytes, where it significantly influences Ca²⁺ signal transduction and the cellular response to stress. Ca²⁺ serves as the most plentiful second messenger within the human body, orchestrating critical regulatory roles across numerous physiological and pathological contexts. It is instrumental in managing aspects of the tumor microenvironment, neurodegenerative conditions, cardiovascular diseases, and metabolic disorders. Maintaining Ca²⁺ homeostasis is crucial for the proper functioning of different subcellular organelles, impacting overall cellular health and activity. Here, we describe the central connection between CAMK2G and subcellular Ca²⁺ homeostasis, highlight the molecular functions of CAMK2G therein, and finally detail the cutting-edge therapeutic strategies targeting CAMK2G.

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CAMK2G在亚细胞Ca2+稳态中的作用：分子机制和治疗靶向。

Ca2+/钙调素依赖性蛋白激酶II （CAMK2）家族由A、B、D和G亚型组成，在解码Ca2+信号中起关键作用，这是细胞通信和功能的重要过程。其中，CAMK2G在各种身体组织中广泛存在，主要表达于神经元和心肌细胞，在这些细胞中，CAMK2G显著影响Ca2+信号转导和细胞对应激的反应。Ca2+作为人体内最丰富的第二信使，在许多生理和病理环境中协调关键的调节作用。它有助于肿瘤微环境、神经退行性疾病、心血管疾病和代谢紊乱的管理。维持Ca2+稳态对不同亚细胞细胞器的正常功能至关重要，影响整体细胞健康和活性。在这里，我们描述了CAMK2G与亚细胞Ca2+稳态之间的中心联系，重点介绍了CAMK2G在其中的分子功能，并详细介绍了针对CAMK2G的前沿治疗策略。

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

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.