O1‐04‐06: Cognitive and Neuroprotective Positive Effects of JNK Inhibition in 5XFAD Transgenic Mice

• DOI: 10.1016/j.jalz.2016.06.315
• Publication Date: 2016-10-17T07:30:54Z
• Authors: Sarah Gourmaud; Priscilla Thomas; Marion Tible; Sylvie Thomasseau; Claire Abadie; Pascal Millet; Claire Paquet; Jacques Hugon
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Alzheimer’s disease (AD) is the most common neurodegenerative disease. AD neuropathologically characterized by extra-neuronal accumulations of beta-amyloid (Aβ) forming senile plaques and intra-neuronal hyperphosphorylated tau proteins, leading to neuroinflammation, synaptic loss neuronal death. Several studies indicate that c-Jun N-terminal kinase (JNK) implicated in pathological features including neurodegeneration. We have investigated for first time 5XFAD mice, disease-modifying therapeutic effect a systemic administration XG-102, small JNK-specific inhibitory peptide currently clinical development other pathologies. Three months-old mice were IV treated every 3 weeks, or 6 months. The outcome XG-102 treatment on cognitive deficits lesions assessed using Y maze, fear-conditioning tests, histological biochemical methods. Chronic months resulted reduction amyloid plaque burden 35% cortex compared with saline-treated mice. After treatment, reduced 32% 46% Maze fear conditioning tests respectively. In addition significant death was detected. conclusion, could be considered as potential candidate evaluated MCI (Mild Cognitive Impairment) mild patients future.