Lipidized analogues of the anorexigenic CART (cocaine- and amphetamine-regulated transcript) neuropeptide show anorexigenic and neuroprotective potential in mouse model of monosodium-glutamate induced obesity
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
39084452
DOI
10.1016/j.ejphar.2024.176864
PII: S0014-2999(24)00553-3
Knihovny.cz E-zdroje
- Klíčová slova
- Alzheimer's disease, CART peptide, Hypothermia, Lipidization, MSG mice, PC12 cells, Tau hyperphosphorylation,
- MeSH
- anorektika farmakologie MeSH
- buňky PC12 MeSH
- fosforylace účinky léků MeSH
- glutamát sodný * MeSH
- kokainem a amfetaminem regulovaný transkript MeSH
- krysa rodu Rattus MeSH
- lipidy chemie krev MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neuroprotektivní látky * farmakologie MeSH
- obezita * metabolismus farmakoterapie MeSH
- proteiny nervové tkáně * metabolismus MeSH
- proteiny tau metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anorektika MeSH
- glutamát sodný * MeSH
- kokainem a amfetaminem regulovaný transkript MeSH
- lipidy MeSH
- neuroprotektivní látky * MeSH
- proteiny nervové tkáně * MeSH
- proteiny tau MeSH
AIMS: This 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. METHODS: We 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. RESULTS: Compared 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. CONCLUSION: Our unique CARTp analogue palm-2-SS-CART(61-102) shows promise as a potent anti-obesity and neuroprotective agent.
Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic
University of Chemistry and Technology Prague Czech Republic
Citace poskytuje Crossref.org
Late-stage labeling of diverse peptides and proteins with iodine-125
