%0 Journal Article %J J Alzheimers Dis %D 2018 %T Brimapitide Reduced Neuronal Stress Markers and Cognitive Deficits in 5XFAD Transgenic Mice. %A Gourmaud, Sarah %A Thomas, Priscilla %A Thomasseau, Sylvie %A Tible, Marion %A Abadie, Claire %A Paquet, Claire %A Hugon, Jacques %X

Alzheimer's disease (AD) is characterized by accumulations of amyloid-β (Aβ42) and hyperphosphorylated tau proteins, associated with neuroinflammation, synaptic loss, and neuronal death. Several studies indicate that c-Jun N-terminal kinase (JNK) is implicated in the pathological features of AD. We have investigated in 5XFAD mice, the therapeutic effects of Brimapitide, a JNK-specific inhibitory peptide previously tested with higher concentrations in another AD model (TgCRND8). Three-month-old 5XFAD and wild-type littermate mice were treated by intravenous injections of low doses (10 mg/kg) of Brimapitide every 3 weeks, for 3 or 6 months (n = 6-9 per group). Cognitive deficits and brain lesions were assessed using Y-maze, fear-conditioning test, and histological and biochemical methods. Chronic treatment of Brimapitide for 3 months resulted in a reduction of Aβ plaque burden in the cortex of 5XFAD treated mice. After 6 months of treatment, cognitive deficits were reduced but also a significant reduction of cell death markers and the pro-inflammatory IL-1β cytokine in treated mice were detected. The Aβ plaque burden was not anymore modified by the 6 months of treatment. In addition to modulating cognition and amyloid plaque accumulation, depending on the treatment duration, Brimapitide seems experimentally to reduce neuronal stress in 5XFAD mice.

%B J Alzheimers Dis %V 63 %P 665-674 %8 2018 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/29660941?dopt=Abstract %R 10.3233/JAD-171099