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 Ca 2+ concentration [(Ca 2+ ) 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.
