Prospects of antidiabetic drugs in the treatment of neurodegenerative disease

Abstract

Neurodegenerative diseases (NDs) stand for a group of disorders characterized by the progressive loss of neurons in the brain and peripheral organs, resulting in motor and cognitive dysfunction. The global prevalence of NDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, is on the rise globally, primarily due to an aging population, positioning NDs as an increasing significant public health concern. Despite intensive research, few effective therapies that prevent or delay ND progression have been developed. Mounting evidence indicates that one of the well‐defined risk factors for NDs is type 2 diabetes mellitus, and insulin resistance has also been proven to be related to cognitive decline. Certain antidiabetic drugs, such as glucagon‐like peptide‐1 receptor agonists, peroxisome proliferator‐activated receptor gamma agonists, and metformin, have shown promise in offering neuroprotective benefits and alleviating ND symptoms beyond their glucose‐lowering effects. Although the exact mechanisms remain elusive, these drugs offer a promising novel strategy for managing cognitive disorders. In this review, we first highlight the benefits and specific neuroprotective effects of multiple antidiabetic drugs and discuss the main mechanisms of action of antidiabetic drugs in treating NDs. These mechanisms include reducing protein aggregation and improving apoptosis, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Finally, we summarize clinical trials evaluating these drugs for treating NDs.

Bio-Nano Synergy in Therapeutic Applications: Drug–Graphene Oxide Nanocomposites for Modulated Acetylcholinesterase Inhibition and Radical Scavenging

“…6 In a recent communication, it has been reported that certain antidiabetic drugs of sulfonylurea class are extremely potent in inhibiting acetylcholinesterase (AChE) activity, suggesting their possible application in the treatment of Alzheimer's disease (AD). 7 Additionally, latest research findings from one of the present research groups indicate that tacrine (TAC), an FDA-approved AD medication, might also be effective in reversing the DNA oxidative stress caused by reactive oxygen species (ROS). 8,9 Intriguingly, in an earlier study, it is shown that the presence of graphene oxide (GO) enhances the anticholinergic effects of TAC, hinting at a synergistic interaction.…”

“…This approach proved especially crucial in the initial phases of the COVID-19 outbreak, where the adaptation of existing medications played a key role in managing the critical health crisis by addressing various symptoms. − Significant examples in this area include the discovery that inhibitors targeting leucine-rich repeat kinase 2 (LRRK2) might be effective for treating Parkinson’s disease (PD) . In a recent communication, it has been reported that certain antidiabetic drugs of sulfonylurea class are extremely potent in inhibiting acetylcholinesterase (AChE) activity, suggesting their possible application in the treatment of Alzheimer’s disease (AD) . Additionally, latest research findings from one of the present research groups indicate that tacrine (TAC), an FDA-approved AD medication, might also be effective in reversing the DNA oxidative stress caused by reactive oxygen species (ROS). , Intriguingly, in an earlier study, it is shown that the presence of graphene oxide (GO) enhances the anticholinergic effects of TAC, hinting at a synergistic interaction …”