Melanocortin MC4 receptor agonists counteract late inflammatory and apoptotic responses and improve neuronal functionality after cerebral ischemia

Interleukin-1β-induced memory reconsolidation impairment is mediated by a reduction in glutamate release and zif268 expression and α-melanocyte-stimulating hormone prevented these effects

“…NDP-MSH can also induce neurogenesis after cerebral ischemia and zif-268 is upregulated in hippocampus as well . Thus, treatment of ischemic stroke with melanocortins is associated with an over-expression of zif-268, promoting neuronal recovery and neurogenesis (Giuliani et al, 2009Spaccapelo et al, 2011). Also, melanocortins protect against progression of Alzheimeŕs disease, an effect associated with hippocampus zif-268 over-expression (Giuliani et al, 2014).…”

Hypothalamic inflammation and food intake regulation during chronic illness

“…These beneficial suppressive effects of ␣-MSH on inflammation may occur via increasing circulating anti-inflammatory cytokines [120]. In addition, ␣-MSH can inhibit pro-inflammatory mediators [121,91,115]. In this way ␣-MSH, via modulation of inflammatory mediators, ican attenuate muscle wasting and progression of cachexia [91].…”

“…Nonetheless, in chronic inflammatory conditions such as cancer, renal failure and heart failure, the use of AgRP or synthetic MC4R antagonists improved food intake [109][110][111][112], but also increased POMC expression and thus possibly ␣MSH [106]. In contrast, administration of ␣MSH or synthetic MC4R agonists, have also shown to be beneficial in chronic inflammation including arthritis [113], inflammatory bowel disease [114] and ischemic stroke [115]. This paradox in beneficial effects by both MC4R agonists and antagonists in chronic inflammatory conditions might be explained by another physiological function of the melanocortin systems next to their direct effect on food intake, namely via their anti-inflammatory actions.…”

“…Elevation of plasma ␣-MSH in chronic inflammatory illnesses could suggest an adaptive response in order to control inflammation [116][117][118]. Both MC4R antagonists [111,119] and agonists [120,121,91,115] act as anti-inflammatory peptides in experimental models for cancer, rheumatoid arthritis and ischemic stroke either centrally of peripherally [122,123]. These beneficial suppressive effects of ␣-MSH on inflammation may occur via increasing circulating anti-inflammatory cytokines [120].…”

The anti-inflammatory selective melanocortin receptor subtype 4 agonist, RO27-3225, fails to prevent acoustic trauma-induced tinnitus in rats

“…These dose regimens were based on those used in previous studies in which significant neuroprotective effects were obtained (Caruso et al, 2007;Giuliani et al, 2006Giuliani et al, , 2007Spaccapelo et al, 2011). Further doses of RO27-3225 were not used due to the prohibitive costs of the drug.…”