Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2021-04-17 , DOI: 10.1007/s10565-021-09605-0 Sagarkumar Patel 1 , Anwesha Das 1 , Payal Meshram 1 , Ayushi Sharma 1 , Arnab Chowdhury 1 , Heena Jariyal 2 , Aishika Datta 3 , Deepaneeta Sarmah 3 , Lakshmi Vineela Nalla 3 , Bichismita Sahu 1 , Amit Khairnar 3 , Pallab Bhattacharya 3 , Akshay Srivastava 4 , Amit Shard 1
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Chronic inflammation (CI) is a primary contributing factor involved in multiple diseases like cancer, stroke, diabetes, Alzheimer’s disease, allergy, asthma, autoimmune diseases, coeliac disease, glomerulonephritis, sepsis, hepatitis, inflammatory bowel disease, reperfusion injury, and transplant rejections. Despite several expansions in our understanding of inflammatory disorders and their mediators, it seems clear that numerous proteins participate in the onset of CI. One crucial protein pyruvate kinase M2 (PKM2) much studied in cancer is also found to be inextricably woven in the onset of several CI’s. It has been found that PKM2 plays a significant role in several disorders using a network of proteins that interact in multiple ways. For instance, PKM2 forms a close association with epidermal growth factor receptors (EGFRs) for uncontrolled growth and proliferation of tumor cells. In neurodegeneration, PKM2 interacts with apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) to onset Alzheimer’s disease pathogenesis. The cross-talk of protein tyrosine phosphatase 1B (PTP1B) and PKM2 acts as stepping stones for the commencement of diabetes. Perhaps PKM2 stores the potential to unlock the pathophysiology of several diseases. Here we provide an overview of the notoriously convoluted biology of CI’s and PKM2. The cross-talk of PKM2 with several proteins involved in stroke, Alzheimer’s, cancer, and other diseases has also been discussed. We believe that considering the importance of PKM2 in inflammation-related diseases, new options for treating various disorders with the development of more selective agents targeting PKM2 may appear.
Graphical abstract
中文翻译：
慢性炎症中的丙酮酸激酶 M2：关键蛋白质-蛋白质相互作用的混合物
慢性炎症 (CI) 是多种疾病的主要促成因素，如癌症、中风、糖尿病、阿尔茨海默病、过敏、哮喘、自身免疫性疾病、乳糜泻、肾小球肾炎、败血症、肝炎、炎症性肠病、再灌注损伤和移植排斥. 尽管我们对炎症性疾病及其介质的理解有了一些扩展，但似乎很明显，许多蛋白质参与了 CI 的发作。在癌症中大量研究的一种关键蛋白质丙酮酸激酶 M2 (PKM2) 也被发现与几个 CI 的发作密不可分。已经发现 PKM2 使用以多种方式相互作用的蛋白质网络在几种疾病中发挥重要作用。例如，PKM2 与表皮生长因子受体 (EGFR) 密切相关，从而导致肿瘤细胞不受控制地生长和增殖。在神经退行性变中，PKM2 与脱嘌呤/脱嘧啶内切脱氧核糖核酸酶 1 (APE1) 相互作用以引发阿尔茨海默病发病机制。蛋白酪氨酸磷酸酶 1B (PTP1B) 和 PKM2 的相互作用是糖尿病发病的垫脚石。也许 PKM2 存储了解锁几种疾病的病理生理学的潜力。在这里，我们概述了 CI 和 PKM2 臭名昭著的复杂生物学。还讨论了 PKM2 与涉及中风、阿尔茨海默氏症、癌症和其他疾病的几种蛋白质的交叉对话。我们认为，考虑到 PKM2 在炎症相关疾病中的重要性，
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