Quote:hmmmm....thoughts from folks in the field?
An interesting paper. NAD+ production is reliant on the reuse of the building blocks of NAD+ after NAD+ is broken down into its components. A protein called eNAMPT blocks this process resulting in much lower NAD+ levels. One way eNAMPT is activated is by binding to CCR5 resulting in lowered NAD and an increase in inflammatory factors. Blocking CCR5 increases levels of NAD+ and lowers inflammation.
Quote:Additionally, blocking TLR4 or CCR5 alleviated the proinflammatory response triggered by eNAMPT. In the VCI mice model, the NAD+ salvage pathway was impaired in PBMCs, which exhibited proinflammatory activity. 5′-phosphoribosyl-pyrophosphate administration restored NAD⁺ levels, suppressed inflammation, and improved cognitive function.
CONCLUSIONS:
Our findings suggest peripheral inflammation driven by impaired NAD+ salvage and elevated eNAMPT levels in PBMCs plays a key role in VCI pathogenesis. Restoring NAD+ homeostasis via 5′-phosphoribosyl-pyrophosphate treatment significantly improved cognition in VCI mice, highlighting NAD+ salvage as a potential therapeutic target.
https://www.ahajournals.org/doi/10.1161/STROKEAHA.125.052431
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