Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model
| Autor: | Aarti Patel, Jack H. Jhamandas, Ryoichi Kimura, Wen Fu, Rania Soudy, Kamaljit Kaur, David Westaway, Jing Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.drug_class Long-Term Potentiation Amylin lcsh:Medicine Drug development Hippocampal formation Pharmacology Hippocampus Neuroprotection Article Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease medicine Animals Receptor lcsh:Science Neuroinflammation Spatial Memory Multidisciplinary business.industry lcsh:R Long-term potentiation Receptor antagonist Peptide Fragments Receptors Islet Amyloid Polypeptide Islet Amyloid Polypeptide Mice Inbred C57BL Neuroprotective Agents 030104 developmental biology Systemic administration Female lcsh:Q business Neurological disorders 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY within the peptides is an essential sequence for preservation of the beneficial effects of the fragments that we report here and constitutes a new pharmacological target. These findings suggest that the amylin receptor antagonism may represent a novel therapy for AD. |
| Databáze: | OpenAIRE |
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