Vascular protective effects of KLF2 on Aβ-induced toxicity: Implications for Alzheimer's disease

Alzheimer's disease (AD) is characterized by excessive amounts of senile plaques and neurofibrillary tangles in the brain, and cerebrovascular pathologies in AD are attracting increasingly more attention. Krüppel-like factor (KLF) 2, a transcription regulator expressed in the mouse embryonic vasculature and involved in the regulation of vascular gene expression, serves as a protective factor in endothelial cells. However, whether KLF2 is involved in neurodegenerative disease, and especially in AD, remains unknown. In the present study, the effects of KLF2 in Aβ-induced neurotoxicity were investigated. Firstly, we found that KLF2 expression decreased at both the RNA and protein levels in AD cases. The following results show that KLF2 was found to be decreased in both a time- and dose-dependent manner in response to Aβ1-42 treatment in primary mouse brain microvascular endothelial cells. Overexpression of KLF2 attenuated Aβ-induced oxidative stress, improved mitochondrial function, and reduced the rate of apoptosis. Furthermore, inhibition of KLF2 promoted Aβ1-42-induced oxidative stress, exacerbated mitochondrial dysfunction, and increased the rate of apoptosis. Our data imply that the promotion of KLF2 expression in cerebral endothelial cells has the potential to be developed as a novel therapeutic strategy for the treatment of cerebral vascular dysfunction in AD.