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In this report, a microchip electrophoresis system with fluorescence detection was used for the quantitation of intracellular carnosine in untreated and stimulated macrophage cell lysates. Carnosine was derivatized with NDA/CN and separated from other endogenous amine reported in macrophage cells. Based on ME-LIF with standard addition, macrophages were estimated to contain a basal intracellular concentration of carnosine (0.079 ± 0.02 nmol per million cells). Carnosine is readily taken up by macrophages in cell culture. Incubation with 20 mM carnosine led to a 600-fold increase in intracellular carnosine compared to basal levels. Furthermore, we have shown that under pro-inflammatory conditions using LPS and IFN-gamma stimulation there is a further 3-fold increase in carnosine uptake in macrophage cells. This suggests that there is a mechanism through which macrophages increase the usage of carnosine during oxidative stress.

By using an in vitro model of AD, we showed that carnosine prevents Aβ-induced oxidative stress in BV-2 microglial cells by decreasing the expression of iNOS and NADPH oxidase and the concentrations of nitric oxide and superoxide anion. Carnosine is also able to decrease the secretion of pro-inflammatory cytokines, simultaneously rescuing IL-10 levels and increasing the synthesis and the release of TGF-β1. Carnosine, through its multimodal mechanism of action, might represent a new pharmacological tool to yield neuroprotection in AD.

By using an in vitro model of AD, we showed that carnosine prevents Aβ-induced oxidative stress in BV-2 microglial cells by decreasing the expression of iNOS and NADPH oxidase and the concentrations of nitric oxide and superoxide anion. Carnosine is also able to decrease the secretion of pro-inflammatory cytokines, simultaneously rescuing IL-10 levels and increasing the synthesis and the release of TGF-β1. Carnosine, through its multimodal mechanism of action, might represent a new pharmacological tool to yield neuroprotection in AD.

This study demonstrated that amylin (and beta-amyloid) might play an important physiological role in promoting the release of neuroprotective factors, namely HspB5 and VEGF, from endothelial cells of the capillary neurovasculature. The data presented in this study confirm the existence of a “cross-talk” between endothelial and neuron-like cells and the relevance of a physiological role of amylin and beta-amyloid, such as the ability to promote the release of neuroprotective factors from endothelial cells.

This study demonstrated that amylin (and beta-amyloid) might play an important physiological role in promoting the release of neuroprotective factors, namely HspB5 and VEGF, from endothelial cells of the capillary neurovasculature. The data presented in this study confirm the existence of a “cross-talk” between endothelial and neuron-like cells and the relevance of a physiological role of amylin and beta-amyloid, such as the ability to promote the release of neuroprotective factors from endothelial cells.