VEGF receptor‐1 modulates amyloid β 1–42 oligomer‐induced senescence in brain endothelial cells

What is it about?

Blood vessels supply oxygen to the brain. In Alzheimer's disease (AD), the normal function of these blood vessels may be compromised due to many different factors including deposition of beta-amyloid (Aβ) around blood vessels and other cardiovascular risk factors. Endothelial cells (ECs), which line the blood vessels in the brain, might play a role in this dysfunction of blood vessels in AD. Recently, our group found that the brain ECs exposed to toxic Aβ1-42 oligomers, or other aging effects, can readily enter a senescence phenotype or a slow death. In all paradigms tested, we showed that VEGFR-1, a growth factor receptor found on ECs protein levels were significantly increased in the senescent ECs, whereas VEGFR-2 levels were significantly decreased. Importantly, we showed that overexpression of VEGFR-1 in brain ECs by itself readily induced senescence, whereas siRNA-mediated knockdown of VEGFR-1 expression was able to prevent senescence. Altered VEGF receptor expression has been documented in brains of Alzheimer's disease (AD) patients and suggests that this pathway may play a role in blood vessel alterations in AD disease pathogenesis. Thus, modulating VEGF receptor expression and signaling events provides us with a novel target to pursue for the prevention and treatment of blood vessel dysfunction in neurodegenerative diseases such as AD.

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