Exploring the Potential of Antidiabetic Agents as Therapeutic Approaches for Alzheimer's and Parkinson's Diseases: A Comprehensive Review

Abstract

Alzheimer's and Parkinson's are two prevalent neurodegenerative disorders with significant societal and healthcare burdens. The search for effective therapeutic approaches to combat these diseases has led to growing interest in exploring the potential of antidiabetic agents. This comprehensive review aims to provide a detailed overview of the current literature on using antidiabetic agents as therapeutic interventions for Alzheimer's and Parkinson's diseases. We discuss the underlying pathological mechanisms of these neurodegenerative diseases, including protein misfolding, inflammation, oxidative stress, and mitochondrial dysfunction. We then delve into the potential mechanisms by which antidiabetic agents may exert neuroprotective effects, including regulation of glucose metabolism and insulin signaling, antiinflammatory effects, modulation of oxidative stress, and improvement of mitochondrial function and bioenergetics. We highlight in vitro, animal, and clinical studies that support the potential benefits of antidiabetic agents in reducing disease pathology and improving clinical outcomes. However, we also acknowledge these agents' limitations, variability in treatment response, and potential side effects. Furthermore, we explore emerging therapeutic targets and novel approaches, such as glucagon-like peptide-1 receptor (GLP-1R) agonists, insulin sensitizer drugs, neuroinflammation-targeted therapies, and precision medicine approaches. The review concludes by emphasizing the need for further research, including largescale clinical trials, to validate the efficacy and safety of antidiabetic agents in treating Alzheimer's and Parkinson's disease. The collaboration between researchers, clinicians, and pharmaceutical companies is essential in advancing the field and effectively treating patients affected by these debilitating neurodegenerative disorders.

The GLP-1 receptor agonist exenatide improves recovery from spinal cord injury by inducing macrophage polarization toward the M2 phenotype

“…Although GLP-1 receptor agonists first came to prominence as a treatment for type-2 diabetes ( Holst, 2004 ; Baggio and Drucker, 2007 ), similar protective effects have been confirmed on cells in the central nervous system, with reports describing the beneficial effects of GLP-1 receptor agonists in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease ( Perry and Greig, 2002 ; Greig et al, 2004 ; Harkavyi et al, 2008 ; Aviles-Olmos et al, 2013 ; Ghasemi et al, 2013 ; Qiu et al, 2016 ; Kong et al, 2023 ; Koshatwar et al, 2023 ), the reduction of ischemic damage and maintenance of the blood–brain barrier after cerebral infarction ( Li et al, 2009 ; Lee et al, 2011 ; Darsalia et al, 2014 ; Shan et al, 2019 ), and the recovery of motor function after SCI ( Li H et al, 2015 ; Li Y et al, 2015 ; Li et al, 2016 ; Sun et al, 2018 ).…”