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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Neuroprotective and restorative properties of the GLP-1/GIP dual agonist DA-JC1 compared with a GLP-1 single agonist in Alzheimer's disease

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Author(s):
Salles, Geisa Nogueira [1, 2] ; Caho, Michele Longoni [1] ; Holscher, Christian [3] ; Pacheco-Soares, Cristina [2] ; Porcionatto, Marimelia [1] ; Lobo, Anderson Oliveira [4]
Total Authors: 6
Affiliation:
[1] Univ Fed Sao Paulo, Dept Biochem, Lab Neurobiol, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo, SP - Brazil
[2] Univ Vale Paraiba, IP&D, Lab Dynam Cellular Compartments, Ave Shishima Hifumi 2911, BR-12244000 Sao Jose Dos Campos, SP - Brazil
[3] Henan Univ Chinese Med, Res & Expt Ctr, Zhengzhou 450000, Henan - Peoples R China
[4] UFPI Fed Univ Piaui, LIMAV Interdisciplinary Lab Adv Mat Mat Sci & Eng, Grad Program, BR-64049550 Teresina, PI - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Neuropharmacology; v. 162, JAN 1 2020.
Web of Science Citations: 0
Abstract

The sister incretins glucagon-like peptide-1 (GLP-1) and glucagon dependent insulinotropic polypeptide (GIP) are growth factors responsible for re-sensitizing insulin signalling. Interestingly, their analogues, originally developed to treat type 2 diabetes (T2D), have demonstrated a range of neuroprotective and neurorestorative properties. Novel peptide GLP-1/GIP dual agonist (DA) shows good effects in diabetic patients, superior to the effects demonstrated by single GIP or GLP-1 mimetics. Furthermore, novel DAs have shown considerable neuroprotection in neurodegenerative models. Here, we investigated the neuroprotective and restorative involvement of the DA DA-JC1 and liraglutide (Lg), a single GLP-1 receptor analogue, in vitro using human neuroblastoma (SH-SY5Y) against oxidative stress induced by oxygen peroxide (H2O2), and in vivo, in a mouse model of Alzheimer's disease (AD), APP/PS1. First, we determined the ideal concentration of the peptides and demonstrated that DA-JC1 protects cells against oxidative stress more than Lg, improving cell viability, normalizing reactive oxygen species (ROS) and attenuating DNA damage generated by H2O2. Moreover, in 10-to-12-months-old APP/PS1 animals treated for 4 weeks, both Lg and DA-JC1 were very efficient in stimulating neurogenesis and reducing some important hallmarks of AD, but DA-JC1 was better than Lg in attenuating crucial neuroinflammatory markers, especially reactive astrocyte, in both wild-type (WT) and APP/PS1 hippocampal regions. Altogether, this study suggests an interactive role of GLP-1 and GIP receptors, enhancing the efficiency of single GLP-1 analogues, especially in attenuating oxidative stress and neuroinflammation. We confirm that combining GLP-1 and GIP results in a variety of beneficial effects, providing key evidences for the development of a promising therapeutic strategy for AD. (AU)

FAPESP's process: 14/20561-0 - Bioreabsorbable polymeric nanodevice as peptide controlled delivery system to Alzheimer's disease therapy
Grantee:Geisa Rodrigues Salles
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)