Therapeutic Potential of FTO Demethylase in Metabolism and Disease Pathways

IF 1.9 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

The Protein Journal Pub Date : 2025-02-09 DOI:10.1007/s10930-025-10250-3

Chaitanya Sree Somala, Selvaraj Sathyapriya, Nagaraj Bharathkumar, Thirunavukarasou Anand, Damal Chandrasekar Mathangi, Konda Mani Saravanan

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引用次数: 0

Abstract

The crucial involvement of the Fat Mass and Obesity-associated (FTO) protein in both metabolic and non-metabolic diseases has been documented since its discovery. This enzyme, known as FTO, is a demethylase that belongs to the 2-oxoglutarate-dependent nucleic acid demethylases. Its primary function is to target N6-methyladenosine (m⁶A) in RNA, which is crucial in regulating RNA stability, processing, and expression. This review facilitates understanding the FTO gene variations linked to Body Mass Index (BMI) and obesity, resulting in increased vulnerability to type 2 diabetes. While prior reviews have already discussed the link between FTO and BMI and its impact on type 2 diabetes, the current review additionally examines the emerging evidence suggesting a direct influence of the FTO gene on metabolism. Additionally, the paper discusses the alternative role of FTO and emphasizes the endophenotypes in neurological circuits and the demethylase function of FTO in neurodegenerative disorders. The review further examines the impact of FTO on several physiological systems and emphasizes the need to study FTO as a potential multitarget for future research and therapies.

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FTO去甲基酶在代谢和疾病途径中的治疗潜力。

脂肪量和肥胖相关蛋白（FTO）自发现以来，在代谢性和非代谢性疾病中都起着至关重要的作用。这种酶被称为FTO，是一种去甲基化酶，属于2-氧戊二酸依赖的核酸去甲基化酶。其主要功能是靶向RNA中的n6 -甲基腺苷（m6A），在调节RNA的稳定性、加工和表达中起着至关重要的作用。本综述有助于了解FTO基因变异与体重指数（BMI）和肥胖之间的关系，从而增加2型糖尿病的易感性。虽然先前的综述已经讨论了FTO与BMI之间的联系及其对2型糖尿病的影响，但当前的综述进一步研究了表明FTO基因对代谢有直接影响的新证据。此外，本文还讨论了FTO的替代作用，并强调了神经回路中的内表型和FTO在神经退行性疾病中的去甲基化酶功能。这篇综述进一步探讨了FTO对几种生理系统的影响，并强调了将FTO作为未来研究和治疗的潜在多靶点进行研究的必要性。

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

The Protein Journal 生物-生化与分子生物学

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

12 months

期刊介绍： The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.