Wednesday, January 15, 2025
1/15/2025
Title: Investigating the role of α5β1 integrin in cognitive dysfunction Key words: eNOS, Vascular Dementia, α5β1 integrin, exercise, therapeutics Abstract: One common element between VaD and COVID-19 is the involvement of α5β1 integrin: a viable receptor for SARS-CoV-2 and whose expression levels increase with age in the bilateral carotid artery stenosis (BCAS) model of VaD. While the ability of SARS-CoV-2 to enter and alter brain function is still being debated, VaD associated cognitive decline is better understood as a result of chronic failure and disruption of the cerebrovasculature. As VaD is a progressive disease, of which both physiology and symptoms worsen over time, the age-associated increase in α5β1 expression may be contributing to the ultimate development of cognitive dysfunction. Moreover, if the binding of SARS-CoV-2 to α5β1 leads to overactivation or increase in expression of the integrin, then COVID-19-associated cognitive decline may occur in a similar manner to that of VaD. Exercise has been shown to improve VaD associated cognitive dysfunction, but the mechanism and whether α5β1 integrin is involved is unknown. Thus, α5β1 integrin’s relationship to cognitive decline and its potential to enhance exercise induced benefits through the following project aims will be explored: using eNOS-deficient mice as a model of VaD, I will correlate integrin α5β1 expression to age-related pathology (Aim 1) and determine if the combined treatment of ATN-161 and exercise provides synergistic improvements to VaD outcome (Aim 2).
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