Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Reduction in Hippocampal Aβ Content During Gly-Pro-Glu Co-Administration Is Associated with Changes in Inflammation and IGF-I Signaling

Laura M. Frago
ORCID logo ,
Emma Burgos-Ramos
ORCID logo ,
María Rodríguez-Pérez
ORCID logo ,
Sandra Canelles
,
Eduardo Arilla-Ferreiro
,
Jesús Argente
ORCID logo ,
Manuela. G. Lopez
ORCID logo ,
Vicente Barrios
* ORCID logo
Version 1 : Received: 17 April 2024 / Approved: 18 April 2024 / Online: 18 April 2024 (10:27:39 CEST)

How to cite: Frago, L.M.; Burgos-Ramos, E.; Rodríguez-Pérez, M.; Canelles, S.; Arilla-Ferreiro, E.; Argente, J.; Lopez, M.G.; Barrios, V. Reduction in Hippocampal Aβ Content During Gly-Pro-Glu Co-Administration Is Associated with Changes in Inflammation and IGF-I Signaling. Preprints 2024, 2024041246. https://doi.org/10.20944/preprints202404.1246.v1 Frago, L.M.; Burgos-Ramos, E.; Rodríguez-Pérez, M.; Canelles, S.; Arilla-Ferreiro, E.; Argente, J.; Lopez, M.G.; Barrios, V. Reduction in Hippocampal Aβ Content During Gly-Pro-Glu Co-Administration Is Associated with Changes in Inflammation and IGF-I Signaling. Preprints 2024, 2024041246. https://doi.org/10.20944/preprints202404.1246.v1

Abstract

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

Keywords

Alzheimer´s disease; cytokines; Gly-Pro-Glu; IGF-I signaling; inflammation

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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