GLP-1 Analogue Liraglutide Attenuates Mutant Huntingtin-Induced Neurotoxicity by Restoration of Neuronal Insulin Signaling

International Journal of Molecular Sciences
Ching-Chi ChangChih-Li Lin

Abstract

Huntington's disease (HD) is a progressive and fatal neurodegenerative disease caused by CAG repeat expansion in the coding region of huntingtin (HTT) protein. The accumulation of mutant HTT (mHTT) contributes to neurotoxicity by causing autophagy defects and oxidative stress that ultimately lead to neuronal death. Interestingly, epidemiologic studies have demonstrated that the prevalence of type-2 diabetes, a metabolic disease mainly caused by defective insulin signaling, is higher in patients with HD than in healthy controls. Although the precise mechanisms of mHTT-mediated toxicity remain unclear, the blockade of brain insulin signaling may initiate or exacerbate mHTT-induced neurodegeneration. In this study, we used an in vitro HD model to investigate whether neuronal insulin signaling is involved in mHTT-mediated neurotoxicity. Our results demonstrated that mHTT overexpression significantly impairs insulin signaling and causes apoptosis in neuronal cells. However, treatment with liraglutide, a GLP-1 analogue, markedly restores insulin sensitivity and enhances cell viability. This neuroprotective effect may be attributed to the contribution of the upregulated expression of genes associated with endogenous antioxidant pathwa...Continue Reading

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Citations

Apr 3, 2019·Brain Injury : [BI]·Damla ErbilHale Yapıcı Eser
May 10, 2019·Frontiers in Aging Neuroscience·Christian Hölscher
Feb 20, 2020·Environmental Science and Pollution Research International·Abdelmagid M ElmatbolyMohamed M Abdel-Daim
Nov 27, 2019·Molecular Metabolism·T D MüllerM H Tschöp
May 5, 2021·The International Journal of Neuroscience·LongQing ZhangXueBi Tian
Aug 28, 2021·International Journal of Molecular Sciences·Ching-Chi ChangChih-Li Lin
Jul 3, 2021·Molecular Neurobiology·Tarapati RanaSimona Bungau

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Methods Mentioned

BETA
transfection
fluorescence microscopy
transgenic
Assay
reverse-transcription PCR
PCR

Software Mentioned

SPSS
ImagePro Plus
Sequence Detection Systems
cellSense V

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