Neuroprotective potential of novel CARTp analogs in the hippocampus of THY-Tau22 mouse model of Tau pathology
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
40578676
DOI
10.1016/j.neuropharm.2025.110578
PII: S0028-3908(25)00284-9
Knihovny.cz E-resources
- Keywords
- Alzheimer's disease, Anorexigenic neuropeptides, CART peptide, Neuroinflammation, THY-Tau22 mice, Tau pathology,
- MeSH
- Astrocytes drug effects pathology metabolism MeSH
- Maze Learning drug effects MeSH
- Hippocampus * drug effects pathology metabolism MeSH
- Cocaine- and Amphetamine-Regulated Transcript Protein MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Neurofibrillary Tangles pathology metabolism drug effects MeSH
- Neuroprotective Agents * pharmacology therapeutic use MeSH
- Spatial Memory drug effects MeSH
- Nerve Tissue Proteins * pharmacology therapeutic use chemistry MeSH
- tau Proteins * genetics metabolism MeSH
- Tauopathies * pathology drug therapy metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cocaine- and Amphetamine-Regulated Transcript Protein MeSH
- Neuroprotective Agents * MeSH
- Nerve Tissue Proteins * MeSH
- tau Proteins * MeSH
Anorexigenic neuropeptides have shown a remarkable potential in the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). One of the strong anorexigenic neuropeptides is called cocaine- and amphetamine-regulated transcript peptide (CARTp), which is the third most abundant transcript in the hypothalamus. Previously, we introduced a novel palmitoylated analog of 2-SS-CART(61-102), a specific analog of natural CART(61-102) with two disulfide bridges, with anorexigenic and neuroprotective properties. This study explores the impact of 2-SS-CART(61-102) and its palmitoylated analog, palm-2-SS-CART(61-102), on the early progression of Tau pathology characteristic of AD, utilizing the THY-Tau22 transgenic mouse model. Chronic subcutaneous treatment with CARTp analogs improved short-term spatial memory in the Y-maze, reduced the number of neurofibrillary tangles (NFT) in the hippocampal CA1 region, and decreased the level of GFAP + astrocytes in the hippocampus of THY-Tau22 mice. Furthermore, treatment with CARTp analogs showed increased levels of synaptic markers in the hippocampus. A beneficial effect on these attributes makes CARTp analogs promising for AD therapy.
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