Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2020; 11(5): 155-164
Published online May 15, 2020. doi: 10.4239/wjd.v11.i5.155
Shared (epi)genomic background connecting neurodegenerative diseases and type 2 diabetes
Valerio Caputo, Andrea Termine, Claudia Strafella, Emiliano Giardina, Raffaella Cascella
Valerio Caputo, Claudia Strafella, Emiliano Giardina, Raffaella Cascella, Department of Biomedicine and Prevention, Tor Vergata University, Rome 00133, Italy
Valerio Caputo, Andrea Termine, Claudia Strafella, Emiliano Giardina, Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, Rome 00142, Italy
Andrea Termine, Experimental and Behavioral Neurophysiology Laboratory, Santa Lucia Foundation, Rome 00142, Italy
Raffaella Cascella, Department of Biomedical Sciences, Catholic University Our Lady of Good Counsel, Tirana 1000, Albania
Author contributions: Caputo V and Termine A conceived of the study, performed the literature search, and wrote the manuscript; Strafella C, Giardina E and Cascella R conceived of the study and revised the manuscript; all authors approved the final version of the article.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Emiliano Giardina, PhD, Associate Professor, Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, Via Ardeatina 354, Rome 00142, Italy. emiliano.giardina@uniroma2.it
Received: December 27, 2019
Peer-review started: December 11, 2019
First decision: January 13, 2020
Revised: February 10, 2020
Accepted: March 22, 2020
Article in press: March 22, 2020
Published online: May 15, 2020
Processing time: 135 Days and 19.9 Hours
Abstract

The progressive aging of populations has resulted in an increased prevalence of chronic pathologies, especially of metabolic, neurodegenerative and movement disorders. In particular, type 2 diabetes (T2D), Alzheimer’s disease (AD) and Parkinson’s disease (PD) are among the most prevalent age-related, multifactorial pathologies that deserve particular attention, given their dramatic impact on patient quality of life, their economic and social burden as well the etiopathogenetic mechanisms, which may overlap in some cases. Indeed, the existence of common triggering factors reflects the contribution of mutual genetic, epigenetic and environmental features in the etiopathogenetic mechanisms underlying T2D and AD/PD. On this subject, this review will summarize the shared (epi)genomic features that characterize these complex pathologies. In particular, genetic variants and gene expression profiles associated with T2D and AD/PD will be discussed as possible contributors to determine the susceptibility and progression to these disorders. Moreover, potential shared epigenetic modifications and factors among T2D, AD and PD will also be illustrated. Overall, this review shows that findings from genomic studies still deserves further research to evaluate and identify genetic factors that directly contribute to the shared etiopathogenesis. Moreover, a common epigenetic background still needs to be investigated and characterized. The evidences discussed in this review underline the importance of integrating large-scale (epi)genomic data with additional molecular information and clinical and social background in order to finely dissect the complex etiopathogenic networks that build up the “disease interactome” characterizing T2D, AD and PD.

Keywords: Type 2 diabetes; Alzheimer’s disease; Parkinson’s disease; Metabolism; Neurodegeneration; Neuroinflammation; Genetic variants; Epigenomic background; Disease interactome

Core tip: Populations’ progressive aging raises important challenges to be faced, including the increased prevalence of metabolic, neurodegenerative and movement disorders, especially of type 2 diabetes, Alzheimer’s disease and Parkinson’s disease. These disorders are characterized by a multifactorial etiology, involving genetic and non-genetic factors, which may overlap. This review will discuss the shared (epi)genomic features, the role of mutually-associated genetic variants, common gene expression profiles and epigenetic background leading to development and progression of such disorders. Overall, this review highlights the importance of characterizing the “disease interactome” in order to establish adequate personalized and preventative healthcare approaches for the ageing populations.