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BBB dysfunction during aging is characterized by an increase in its permeability and phenotypic alterations of brain endothelial cells (BECs) including dysregulation of tight junction's expression. Here we have investigated the role of BEC senescence in the dysfunction of the BBB. Our results suggest that the transition from young to aged BBB is mediated, at least in part by BEC senescence. [ABSTRACT FROM AUTHOR]

The increase in the available G protein-coupled receptor (GPCR) structures has been pivotal in helping to understand their activation process. However, the role of protonation-conformation coupling in GPCR activation still needs to be clarified. We studied the protonation behavior of the highly conserved Asp 2.50 residue in five different class A GPCRs (active and inactive conformations) using a linear response approximation (LRA) p K a calculation protocol. We observed consistent differences (1.3 p K units) for the macroscopic p K a values between the inactive and active states of the A2AR and B2AR receptors, indicating the protonation of Asp 2.50 during GPCR activation. This process seems to be specific and not conserved, as no differences were observed in the p K a values of the remaining receptors (CB1R, NT1R, and GHSR).