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

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.

Dopamine- and Grape-Seed-Extract-Loaded Solid Lipid Nanoparticles: Interaction Studies between Particles and Differentiated SH-SY5Y Neuronal Cell Model of Parkinson’s Disease

“…To date, the primary approach to pharmacological therapy in PD has mainly focused on the administration of molecules aimed at alleviating motor symptoms [6]; furthermore, it is known that aS dyshomeostasis plays an important role in both the onset and progression of PD. A promising avenue to pursue in the formulation of new therapies is represented by the synergistic effects of antioxidant and cytoprotective substances [37].…”

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts

“…Remarkably, since 1990, their prevalence has surged by 155.5%, 132.2%, and 129.7%, respectively. Presently, the global tally of diagnosed cases includes over 590 million individuals with OA, more than 530 million with T2DM, and exceeding 8.5 million with PD [2][3][4][5]. These conditions, which often occur concurrently in the same individual, present formidable challenges to healthcare systems and significantly compromise the QoL for those affected.…”