| First Author | Wu L | Year | 2021 |
| Journal | Aging Cell | Volume | 20 |
| Issue | 6 | Pages | e13371 |
| PubMed ID | 33955647 | Mgi Jnum | J:311343 |
| Mgi Id | MGI:6718340 | Doi | 10.1111/acel.13371 |
| Citation | Wu L, et al. (2021) Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer's disease. Aging Cell 20(6):e13371 |
| abstractText | Alzheimer's disease (AD) is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited. Over-activation of N-methyl-D-aspartate (NMDA) receptors, amyloid beta (Abeta) aggregation, a decrease in cerebral blood flow (CBF), and downstream pathological events play important roles in the disease progression of AD. In the present study, MN-08, a novel memantine nitrate, was found to inhibit Abeta accumulation, prevent neuronal and dendritic spine loss, and consequently attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice (for a 6-month preventative course) and in the 8-month-old triple-transgenic (3xTg-AD) mice (for a 4-month therapeutic course). In vitro, MN-08 could bind to and antagonize NMDA receptors, inhibit the calcium influx, and reverse the dysregulations of ERK and PI3K/Akt/GSK3beta pathway, subsequently preventing glutamate-induced neuronal loss. In addition, MN-08 had favorable pharmacokinetics, blood-brain barrier penetration, and safety profiles in rats and beagle dogs. These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD. |
