Siddiqui M Sarim, Shahi Mehdi H, Castresana Javier S
Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, India.
Department of Biochemistry and Genetics, University of Navarra School of Sciences, Pamplona 31008, Spain.
J Clin Transl Sci. 2024 Aug 19;8(1):e96. doi: 10.1017/cts.2024.536. eCollection 2024.
Adenylate kinases (AKs) are important enzymes involved in cellular energy metabolism. Among AKs, AK5 (adenylate kinase 5), a cytosolic protein, is emerging as a significant contributor to various diseases and cellular processes. This comprehensive review integrates findings from various research groups on AK5 since its discovery, shedding light on its multifaceted roles in nucleotide metabolism, energy regulation, and cellular differentiation. We investigate its implications in a spectrum of diseases, including autoimmune encephalitis, epilepsy, neurodegenerative disorders such as Alzheimer's and Parkinson's, diabetes, lower extremity arterial disease, celiac disease, and various cancers. Notably, AK5's expression levels and methylation status have been associated with cancer progression and patient outcomes, indicating its potential as a prognostic indicator. Furthermore, AK5 is implicated in regulating cellular processes in breast cancer, gastric cancer, colorectal carcinoma, prostate cancer, and colon adenocarcinoma, suggesting its relevance across different cancer types. However, a limitation lies in the need for more robust clinical validation and a deeper understanding of AK5's precise mechanisms in disease pathogenesis, despite its association with various pathophysiological conditions. Nonetheless, AK5 holds promise as a therapeutic target, with emerging evidence suggesting its potential in therapy development.
腺苷酸激酶（AKs）是参与细胞能量代谢的重要酶类。在AKs中，胞质蛋白AK5（腺苷酸激酶5）正逐渐成为多种疾病和细胞过程的重要促成因素。这篇综述综合了自AK5发现以来各研究小组的研究结果，揭示了其在核苷酸代谢、能量调节和细胞分化中的多方面作用。我们研究了它在一系列疾病中的影响，包括自身免疫性脑炎、癫痫、阿尔茨海默病和帕金森病等神经退行性疾病、糖尿病、下肢动脉疾病、乳糜泻以及各种癌症。值得注意的是，AK5的表达水平和甲基化状态与癌症进展和患者预后相关，表明其作为预后指标的潜力。此外，AK5参与调节乳腺癌、胃癌、结直肠癌、前列腺癌和结肠腺癌中的细胞过程，这表明它在不同癌症类型中都具有相关性。然而，尽管AK5与各种病理生理状况有关，但仍存在局限性，即需要更有力的临床验证以及对其在疾病发病机制中精确机制的更深入理解。尽管如此，AK5有望成为治疗靶点，新出现的证据表明其在治疗开发中的潜力。
