The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia

Sharon Negri; Madison Sanford; Helen Shi; Stefano Tarantini

doi:10.3389/fnagi.2023.1149820

The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia

Front Aging Neurosci. 2023 Mar 20:15:1149820. doi: 10.3389/fnagi.2023.1149820. eCollection 2023.

Authors

Sharon Negri^{1

2

3}, Madison Sanford^{1

2

3}, Helen Shi¹, Stefano Tarantini^{1

2

3

4}

Affiliations

¹ Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
² Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
³ International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary.
⁴ Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.

Abstract

Transient receptor potential (TRP) proteins are part of a superfamily of polymodal cation channels that can be activated by mechanical, physical, and chemical stimuli. In the vascular endothelium, TRP channels regulate two fundamental parameters: the membrane potential and the intracellular Ca²⁺ concentration [(Ca²⁺)_i]. TRP channels are widely expressed in the cerebrovascular endothelium, and are emerging as important mediators of several brain microvascular functions (e.g., neurovascular coupling, endothelial function, and blood-brain barrier permeability), which become impaired with aging. Aging is the most significant risk factor for vascular cognitive impairment (VCI), and the number of individuals affected by VCI is expected to exponentially increase in the coming decades. Yet, there are currently no preventative or therapeutic treatments available against the development and progression of VCI. In this review, we discuss the involvement of endothelial TRP channels in diverse physiological processes in the brain as well as in the pathogenesis of age-related VCI to explore future potential neuroprotective strategies.

Keywords: Geroscience; aging; cognitive dysfunction; dementia; lifestyle intervention; neurodegeneration; neurovascular coupling.

Publication types

Review

Abstract

Publication types

Grants and funding