Dustin Christopher M, Shiva Sruti S, Vazquez Alberto, Saeed Anum, Pascoal Tharick, Cifuentes-Pagano Eugenia, Pagano Patrick J
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 1526, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 1526, USA.
Redox Biol. 2024 Dec;78:103433. doi: 10.1016/j.redox.2024.103433. Epub 2024 Nov 15.
Alzheimer's Disease (AD), and related dementias, represent a growing concern for the worldwide population given the increased numbers of people of advanced age. Marked by significant degradation of neurological tissues and critical processes, in addition to more specific factors such as the presence of amyloid plaques and neurofibrillary tangles in AD, robust discussion is ongoing regarding the precise mechanisms by which these diseases arise. One of the major interests in recent years has been the contribution of reactive oxygen species (ROS) and, particularly, the contribution of the ROS-generating NADPH Oxidase proteins. NADPH Oxidase 2 (NOX2), the prototypical member of the family, represents a particularly interesting target for study given its close association with vascular and inflammatory processes in all tissues, including the brain, and the association of these processes with AD development and progression. In this review, we discuss the most relevant and recent work regarding the contribution of NOX2 to AD progression in neuronal, microglial, and cerebrovascular signaling. Furthermore, we will discuss the most promising NOX2-targeted therapeutics for potential AD management and treatment.
鉴于老年人口数量的增加，阿尔茨海默病（AD）及相关痴呆症已成为全球日益关注的问题。这些疾病的特征是神经组织和关键过程的显著退化，除了AD中存在淀粉样斑块和神经原纤维缠结等更具体的因素外，关于这些疾病产生的确切机制的讨论也在热烈进行。近年来的一个主要研究兴趣是活性氧（ROS）的作用，特别是产生活性氧的NADPH氧化酶蛋白的作用。该家族的典型成员NADPH氧化酶2（NOX2）是一个特别有趣的研究靶点，因为它与包括大脑在内的所有组织中的血管和炎症过程密切相关，且这些过程与AD的发生和发展有关。在这篇综述中，我们讨论了关于NOX2在神经元、小胶质细胞和脑血管信号传导中对AD进展的作用的最相关和最新的研究。此外，我们还将讨论最有前景的针对NOX2的治疗方法，用于潜在的AD管理和治疗。
