Perez Lao Efrain J, Fagerli Eric, Ferrier Fernando, Young Juan I, Perez-Pinzon Miguel A
Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA.
Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA.
J Neurochem. 2025 Sep;169(9):e70193. doi: 10.1111/jnc.70193.
Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role as a transcription factor at the heart of cellular defense mechanisms against oxidative stress, orchestrating a suite of cytoprotective genes. This review places particular emphasis on the interplay between Nrf2 and Sirtuins-NAD-dependent deacetylases integral to redox regulation, metabolic control, and neuroprotection. We highlight how these proteins cooperate to regulate oxidative defense and cellular metabolism, with a particular focus on brain physiology and resilience. We briefly touch on the regulatory influence of specific microRNAs (e.g., miR-126, miR-34a) as emerging modulators of this pathway. Through this review, we aim to consolidate insights into Nrf2-Sirtuin crosstalk, particularly in the context of brain health, and highlight potential therapeutic strategies including pharmacological agents, miRNA modulators, and ischemic preconditioning mimetics. This work aims to inspire further investigation and translational advances in the treatment of oxidative stress-related neurological disorders.
核因子红细胞2相关因子2（Nrf2）作为转录因子在细胞对抗氧化应激的防御机制核心中发挥着关键作用，协调一系列细胞保护基因。本综述特别强调Nrf2与去乙酰化酶（Sirtuins）之间的相互作用，去乙酰化酶是氧化还原调节、代谢控制和神经保护所必需的NAD依赖性脱乙酰酶。我们重点介绍了这些蛋白质如何协同调节氧化防御和细胞代谢，特别关注脑生理学和恢复力。我们简要提及特定微小RNA（如miR-126、miR-34a）作为该途径新兴调节因子的调节作用。通过本综述，我们旨在巩固对Nrf2-去乙酰化酶串扰的认识，特别是在脑健康背景下，并强调潜在的治疗策略，包括药物制剂、miRNA调节剂和缺血预处理模拟物。这项工作旨在激发在氧化应激相关神经疾病治疗方面的进一步研究和转化进展。
