| First Author | Porte B | Year | 2020 |
| Journal | Brain Res | Volume | 1727 |
| Pages | 146587 | PubMed ID | 31811838 |
| Mgi Jnum | J:283384 | Mgi Id | MGI:6386527 |
| Doi | 10.1016/j.brainres.2019.146587 | Citation | Porte B, et al. (2020) Dose-dependent neuroprotective effect of the JNK inhibitor Brimapitide in 5xFAD transgenic mice. Brain Res 1727:146587 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative disease mainly affecting old people. According to the "amyloid cascade hypothesis", the accumulation of Abeta oligomers could lead to kinase activation and Tau phosphorylation. Activated kinases include c-Jun N-terminal kinase (JNK) and previous studies highlighted the beneficial effects of the JNK-specific inhibitor Brimapitide (10 mg/kg) in 5xFAD transgenic mice. Our aim was to evaluate the effects of decreasing doses of Brimapitide on cognition and neurodegeneration in early treated 5xFAD mice. Three month-old 5xFAD were intravenously treated for 6 months with either Brimapitide (3 mg/kg or 0.3 mg/kg) or Nacl. Cognition and amyloid burden, neuronal and synaptic impairments were evaluated. Low doses of Brimapitide (0.3 mg/kg) reduced neuronal degeneration and improved cognition in treated mice compared to non-treated mice. Amyloid burden and synaptic degeneration only decreased with the 3 mg/kg dose. This JNK inhibitor can afford neuroprotection but with a differential effect on amyloid deposition in 5xFAD mice. Brimapitide might partially prevent ongoing neurodegeneration in 5xFAD mice. |
