Is It All Connected? Repurposing Diabetes Drugs for Neuroprotection
With Alzheimer’s and Brain Awareness Month just over, it's an opportune time to examine the growing evidence of connections between type 2 diabetes and Alzheimer’s disease. There has been increasing research analyzing whether diabetes drugs, in particular, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon like peptide-1 (GLP-1) agonists, offer neuroprotective effects in cognitive diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Insulin resistance, a hallmark of type 2 diabetes, seems to also play a role in dementia. GLP-1 is expressed after eating and helps regulate carbohydrate metabolism, insulin production, and appetite; however, the GLP-1 incretins are mostly metabolized by the DPP-4 enzyme. DPP-4 inhibitors prevent the degradation action of the DPP-4 enzyme while GLP-1 receptor agonists (GLP-1RA) promote GLP-1 secretion. Both assist in insulin secretion and, in turn, glucose reduction. A few new reviews look at the possibility of repurposing these traditional diabetes drugs into treatments for neurodegenerative diseases. Repositioning a current drug greatly reduces the costs and timeline of drug development. Liraglutide, a GLP-1RA with resistance to DPP-4 degradation, may have an impact on clearing amyloid beta (Aß) protein through its binding to the GLP-1 receptor and resulting P13K/MAPK activation, whereas insulin did not elicit the same response.1,2. Further studies are justified in this exciting, new application of GLP-1RA and DDP-4 inhibitors in neuroprotection.
- M. Wicinski, et al., International Journal of Molecular Sciences, 20, 1050 (2019).
- S.A. Mousa & B.M. Ayoub, Neural Regen Res., 14(5), 745 (2019).
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