Abstract
AimsThis study investigates the neuroprotective effects of lipidized analogues of 2-SS-CART(61–102) derived from anorexigenic neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) in light of the link between obesity, its comorbidities, and the development of Alzheimer's disease. MethodsWe introduce novel lipidized analogues derived from 2-SS-CART(61–102), a specific analogue of natural CART(61–102), with two disulfide bridges. Using hypothermic PC12 cells, we tested the effect of the most potent analogues on Tau phosphorylation. We further described the anorexigenic and neuroprotective potential of subcutaneously (SC) injected lipidized CARTp analogue in a mouse model with prediabetes and obesity induced by neonatal monosodium glutamate (MSG) administration. ResultsCompared to the non-lipidized 2-SS-CART(61–102), all lipidized analogues exhibited a potent binding affinity to PC12 cells and enhanced in vitro stability in rat plasma. Two most potent lipidized analogues attenuated hypothermia-induced Tau hyperphosphorylation at multiple epitopes. Subsequently, chronic SC treatment with palm-2-SS-CART(61–102) significantly decreased body weight and food intake, improved metabolic parameters, decreased level of pTau and increased neurogenesis in hippocampi of obese MSG mice. ConclusionOur unique CARTp analogue palm-2-SS-CART(61–102) shows promise as a potent anti-obesity and neuroprotective agent.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have