Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease

Marco Greco; Anas Munir; Debora Musarò; Chiara Coppola; Michele Maffia

doi:10.3389/fnins.2023.1244022

Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease

Front Neurosci. 2023 Nov 3:17:1244022. doi: 10.3389/fnins.2023.1244022. eCollection 2023.

Authors

Marco Greco^#¹, Anas Munir^#^{1

2}, Debora Musarò¹, Chiara Coppola^{1

2}, Michele Maffia¹

Affiliations

¹ Department of Biological and Environmental Science and Technology, University of Salento, Lecce, Italy.
² Department of Mathematics and Physics "E. De Giorgi", University of Salento, Lecce, Italy.

^# Contributed equally.

Abstract

Parkinson's disease (PD) is a predominantly idiopathic pathological condition characterized by protein aggregation phenomena, whose main component is alpha-synuclein. Although the main risk factor is ageing, numerous evidence points to the role of type 2 diabetes mellitus (T2DM) as an etiological factor. Systemic alterations classically associated with T2DM like insulin resistance and hyperglycemia modify biological processes such as autophagy and mitochondrial homeostasis. High glucose levels also compromise protein stability through the formation of advanced glycation end products, promoting protein aggregation processes. The ability of antidiabetic drugs to act on pathways impaired in both T2DM and PD suggests that they may represent a useful tool to counteract the neurodegeneration process. Several clinical studies now in advanced stages are looking for confirmation in this regard.

Keywords: Parkinson’s disease; alpha-synuclein; autophagy; hyperglycemia; insulin-resistance; islet amyloid peptide protein; type 2 diabetes mellitus.

Publication types

Review

Grants and funding

This research was funded by: (i) Italian Ministry of University and Research thanks to the PRIN 2017 project (MIUR) prot. 2017J92TM5 “enhancement of autophagy for the therapy of liver diseases” and to the innovative PhD position made available to AM; (ii) Apulia Region thanks to the post-doc position of the POC PUGLIA FESR ESF 2014/2020 entitled “PaRTiRe - Parkinson’s research through the voice” “Riparti project” made available to MG; (iii) Concorde Project, with grant PNRA18_0 0071_Prot. 20891.21-11-2019, assigned to Michele Samaja, Department of Health Sciences, University of Milan, Milan, Italy. We must also thank the “Alessia Pallara” Foundation for its constant economic support to our Physiology Lab at University of Salento.