Gupta Anannya, Chakole Swarupa, Agrawal Suyash, Khekade Harshal, Prasad Roshan, Lohakare Tejaswee, Wanjari Mayur
Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND.
Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND.
Cureus. 2023 Aug 16;15(8):e43609. doi: 10.7759/cureus.43609. eCollection 2023 Aug.
Necroptosis is a regulated form of cell death that has gained increasing attention in recent years. It plays a significant role in various physiological and pathological processes, including renal health and disease. This review article provides an overview of necroptosis as a regulated cell death pathway and explores its implications in renal physiology and renal diseases. The molecular signaling pathways involved in necroptosis, including the key players such as receptor-interacting protein kinases (RIPKs) and mixed lineage kinase domain-like protein (MLKL), are discussed in detail. The crosstalk between necroptosis and other cell death pathways, particularly apoptosis, is explored to understand the interplay between these processes in renal cells. In normal physiological conditions, necroptosis has been found to play a crucial role in renal development and tissue homeostasis. However, dysregulated necroptosis can contribute to tissue damage, inflammation, and fibrosis in renal diseases. The review highlights the involvement of necroptosis in acute kidney injury, chronic kidney disease, and renal transplant rejection, elucidating the underlying pathophysiological mechanisms and consequences. The therapeutic targeting of necroptosis in renal diseases is an emerging area of interest. Current and emerging strategies to modulate necroptosis, including the inhibition of key mediators and regulators, are discussed here. Additionally, the potential therapeutic targets and inhibitors of necroptosis, along with preclinical and clinical studies exploring their efficacy, are reviewed.
坏死性凋亡是一种受调控的细胞死亡形式，近年来受到越来越多的关注。它在包括肾脏健康和疾病在内的各种生理和病理过程中发挥着重要作用。这篇综述文章概述了坏死性凋亡作为一种受调控的细胞死亡途径，并探讨了其在肾脏生理学和肾脏疾病中的意义。详细讨论了参与坏死性凋亡的分子信号通路，包括关键分子如受体相互作用蛋白激酶（RIPKs）和混合谱系激酶结构域样蛋白（MLKL）。探讨了坏死性凋亡与其他细胞死亡途径，特别是细胞凋亡之间的相互作用，以了解这些过程在肾细胞中的相互影响。在正常生理条件下，坏死性凋亡已被发现对肾脏发育和组织稳态起着关键作用。然而，坏死性凋亡失调可导致肾脏疾病中的组织损伤、炎症和纤维化。该综述强调了坏死性凋亡在急性肾损伤、慢性肾脏病和肾移植排斥反应中的作用，阐明了潜在的病理生理机制和后果。针对肾脏疾病中坏死性凋亡的治疗靶向是一个新兴的研究领域。本文讨论了目前和新出现的调节坏死性凋亡的策略，包括抑制关键介质和调节因子。此外，还综述了坏死性凋亡的潜在治疗靶点和抑制剂，以及探索其疗效的临床前和临床研究。
