Abstract
Alzheimer’s disease (AD) is one of the main human dementias around the world which is constantly increasing every year due to several factors (age, genetics, environment, etc.) and there are no prevention or treatment options to cure it. AD is characterized by memory loss associated with oxidative stress (OS) in brain cells (neurons, astrocytes, microglia, etc.). OS can be produced by amyloid beta (Aβ) protein aggregation and its interaction with metals, mitochondrial damage and alterations between antioxidants and oxidant enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. NADPH oxidase produces reactive oxygen species (ROS) and it is overexpressed in AD, producing large amounts of superoxide anions and hydrogen peroxide which damage brain cells and the vasculature. In addition, it has been reported that NADPH oxidase causes an imbalance of pH which could also influence in the amyloid beta (Aβ) production. Therefore, NADPH oxidase had been proposed as a therapeutic target in AD. However, there are no drugs for AD treatment such as an NADPH oxidase inhibitor despite great efforts made to stabilize the ROS production using antioxidant molecules. So, in this work, we will focus our attention on NADPH oxidase (NOX2 and NOX4) in AD as well as in AD models and later discuss the use of NADPH oxidase inhibitor compounds in AD.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss due to multiple factors, including the generation of reactive oxygen species (ROS) [1,2].ROS can be produced at the brain level by various pathways: a decrease in antioxidant enzymes or an increase in oxidant enzymes
In rat and mouse models without or with some treatment in which the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is shown, the expression and activity of NOX2 and NOX4 have been reported in the hippocampus and cortex, important areas of the brain related to memory and learning [85]
GSK2795039 was proposed as an NOX2 selective inhibitor, recently it was reported that GSK2795039 inhibits NOX2 and NOX4, with the effect being more pronounced for NOX2 (>60%) [131]
Summary
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss due to multiple factors, including the generation of reactive oxygen species (ROS) [1,2]. ROS can damage different biomolecules, such as lipids and proteins, and cause DNA-producing biomolecular damage capable of causing neurodegeneration that causes the cognitive deficit and memory loss of patients with AD. This fact could be more evident in some persons that develop sporadic AD, which results from the combination of environmental factors and genetic risk, representing more than 95% of all AD cases [4]. The oxidative stress (OS) generated due to ROS from the production of superoxide anions (O2 − ) and hydrogen peroxide (H2 O2 ) by NADPH oxidase is one of the main causes of cerebrovascular damage and neurodegeneration in AD [7,8]
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