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

Authored by sciencedirect.com and submitted by mvea

Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Previous studies have shown that the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) that have anti-diabetic properties show very promising effects in animal models of AD. Glucagon (Gcg) is a hormone and growth-factor, and the Gcg receptor is expressed in the brain. Here we test the effects of a triple receptor agonist (TA), which activates GIP-1, GIP and glucagon receptors at the same time. In the present study, the effects of the TA were evaluated in the APP/PS1 transgenic mouse model of AD. The TA was injected once-daily (10 nmol/kg i.p.) for two months. The results showed that treatment with TA significantly reversed the memory deficit in the APP/PS1 mice in a spatial water maze test. Moreover, the drug reduced levels of the mitochondrial pro-apoptotic signaling molecule BAX, increased the anti-apoptotic signaling molecule Bcl-2 and enhanced the levels of BDNF, a key growth factor that protects synaptic function. Levels of synaptophysin were enhanced, demonstrating protection from synaptic loss that is observed in AD. Neurogenesis in the dentate gyrus was furthermore enhanced as shown in the increase of doublecortin positive cells. Furthermore, TA treatment reduced the total amount of β-amyloid, reduced neuroinflammation (activated microglia and astrocytes), and oxidative stress in the cortex and hippocampus. Thus, these findings show that novel TAs are a promising lead for the design of future treatment strategies in AD.

BeforeTheStormz on January 1st, 2018 at 15:20 UTC »

Does this imply a connection between diabetes and Alzheimer's?

austen1996 on January 1st, 2018 at 13:50 UTC »

A lack of neurogenesis has also been linked to depression, I wonder if this drug could therefore have other applications beyond treating Alzheimer's.

mvea on January 1st, 2018 at 11:14 UTC »

I’ve deliberately linked to the open access, full-text journal article. Some of you may prefer the official press release, which is located here: https://www.eurekalert.org/pub_releases/2017-12/lu-dd122017.php