Increased Expression of Autophagy-Related Genes in Alzheimer’s Disease—Type 2 Diabetes Mellitus Comorbidity Models in Cells

Clara Vianello, Marco Salluzzo, Daniela Anni, Diana Boriero, Mario Buffelli and Lucia Carboni ()
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Clara Vianello: Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Via Irnerio 48, 40126 Bologna, Italy
Marco Salluzzo: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Irnerio 48, 40126 Bologna, Italy
Daniela Anni: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
Diana Boriero: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
Mario Buffelli: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy
Lucia Carboni: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Irnerio 48, 40126 Bologna, Italy

IJERPH, 2023, vol. 20, issue 5, 1-17

Abstract: The association between Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) has been extensively demonstrated, but despite this, the pathophysiological mechanisms underlying it are still unknown. In previous work, we discovered a central role for the autophagy pathway in the common alterations observed between AD and T2DM. In this study, we further investigate the role of genes belonging to this pathway, measuring their mRNA expression and protein levels in 3xTg-AD transgenic mice, an animal model of AD. Moreover, primary mouse cortical neurons derived from this model and the human H4Swe cell line were used as cellular models of insulin resistance in AD brains. Hippocampal mRNA expression showed significantly different levels for Atg16L1 , Atg16L2 , GabarapL1 , GabarapL2 , and Sqstm1 genes at different ages of 3xTg-AD mice. Significantly elevated expression of Atg16L1 , Atg16L2 , and GabarapL1 was also observed in H4Swe cell cultures, in the presence of insulin resistance. Gene expression analysis confirmed that Atg16L1 was significantly increased in cultures from transgenic mice when insulin resistance was induced. Taken together, these results emphasise the association of the autophagy pathway in AD-T2DM co-morbidity, providing new evidence about the pathophysiology of both diseases and their mutual interaction.

Keywords: Alzheimer’s disease; type 2 diabetes mellitus; autophagy; ATG16L1; ATG16L2; GABARAP; GABARAPL1; GABARAPL2; SQSTM1; neuronal cultures (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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