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
Sruti S. Shiva
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
Alberto Vazquez
Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 1526, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 1526, USA
Anum Saeed
Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA
Tharick Pascoal
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA
Eugenia Cifuentes-Pagano
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
Patrick J. Pagano
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; Corresponding author. Department of Pharmacology & Chemical Biology and Vascular Medicine Institute, University of Pittsburgh, 203 Lothrop Street, BST-E1247, Pittsburgh, PA, 15261, USA.
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.
