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 () 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.

References:

  1. M. Wicinski, et al., International Journal of Molecular Sciences, 20, 1050 (2019).
  2. S.A. Mousa & B.M. Ayoub, Neural Regen Res., 14(5), 745 (2019).

Additional reading on this topic:

DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling.

Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer's disease.

Industry News , Biologically Active Peptides , Diabetes , Neuroscience

Denise Karounos

See all articles from Denise Karounos

Denise Karounos joined Peptides International in October 2016. After completing her BS in chemistry from West Virginia University, she spent time as an organic chemist at Bachem Bioscience synthesizing peptides and amino acid derivatives. Denise has experience with both solid and solution-phase peptide synthesis, and has worked under both research and cGMP settings. After completing her MBA from Saint Joseph’s University, Denise transitioned into product management of peptides and amino acid derivatives. In her marketing role, she had many duties including but not limited to product management, market research, creating and producing marketing materials, handling US catalog distribution and customer database, email marketing, quoting and inside sales, sales calls, and coordinating and attending trade conferences. 

At PI, Denise's duties encompass both sales and marketing, bringing to bear her extensive lab and sales support experience. Contact her today and see how Denise can assist you with your peptide research project.