CRTC1 is a potential target to delay aging-induced cognitive deficit by protecting the integrity of the blood-brain barrier via inhibiting inflammation

Abstract

Aging can cause attenuation in the functioning of multiple organs, and blood-brain barrier (BBB) breakdown could promote the occurrence of disorders of the central nervous system during aging. Since inflammation is considered to be an important factor underlying BBB injury during aging, vascular endothelial cell senescence serves as a critical pathological basis for the destruction of BBB integrity. In the current review, we have first introduced the concepts related to aging-induced cognitive deficit and BBB integrity damage. Thereafter, we reviewed the potential relationship between disruption of BBB integrity and cognition deficit and the role of inflammation, vascular endothelial cell senescence, and BBB injury. We have also briefly introduced the function of CREB-regulated transcription co-activator 1 (CRTC1) in cognition and aging-induced CRTC1 changes as well as the critical roles of CRTC1/cyclooxygenase-2 (COX-2) in regulating inflammation, endothelial cell senescence, and BBB injury. Finally, the underlying mechanisms have been summarized and we propose that CRTC1 could be a promising target to delay aging-induced cognitive deficit by protecting the integrity of BBB through promoting inhibition of inflammation-mediated endothelial cell senescence.

The neutrophil-to-lymphocyte ratio is associated with mild cognitive impairment in community-dwelling older women aged over 70 years: a population-based cross-sectional study

“…Systemic inflammation can promote aging-like brain changes, which may lead to a trajectory of cognitive decline. In addition, aging can affect cholinergic regulation of the nervous system and reduce acetylcholine activity, thereby activating multiple signaling pathways that regulate oxidative stress, inflammation of the nervous system, and interference with brain neurotrophic factors ( Wang et al, 2023 ). Therefore, in age-related and pathological conditions, the accumulation of cell aging in peripheral tissues may lead to impaired memory function.…”

“…Frontiers in Aging 06 frontiersin.org signaling pathways that regulate oxidative stress, inflammation of the nervous system, and interference with brain neurotrophic factors (Wang et al, 2023). Therefore, in age-related and pathological conditions, the accumulation of cell aging in peripheral tissues may lead to impaired memory function.…”

Chronic but not acute nicotine treatment ameliorates acute inflammation‐induced working memory impairment by increasing CRTC1 and HCN2 in adult male mice

“…7 However, it is not known how LPS induced WM deficiency and there is currently no effective strategy for inflammation-induced WM deficiency. CREB-regulated transcription coactivator 1 (CRTC1), a key regulator of gene transcription driven by the cAMP response element (CRE), 8 plays essential roles in memory consolidation 9 and reconsolidation. 10 CRTC1 dysfunction is associated with memory deficiency caused by ischemic stroke, 11 Alzheimer's disease, 12 and LPS.…”