| Summary: | The brain is one of the most exquisite organs in the body with high metabolic demands, and requires a tight regulation of the surrounding environment. This tight control is exerted by the neurovascular unit (NVU) comprising different cell types, where endothelial cells play the commander-in-chief role. Thus, it is assumable that even slight perturbations in NVU might affect, in some cases irreversibly, brain homeostasis and health. In this line, recent findings support the two-hit vascular hypothesis for neurodegenerative conditions, where vascular dysfunction underlies the development of neurodegenerative diseases, such as Alzheimer’s disease (AD). Knowing that endothelial cells are rich in mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, two major reactive oxygen species (ROS) sources, this review aims to gather information on how oxidative stress is in the front line of vascular alterations observed in brain aging and neurodegenerative conditions, particularly AD. Also, a brief discussion about the therapeutic strategies aimed to protect against cerebrovascular diseases is included.
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