title: A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer's disease.
abstract: A small molecule named ISRIB has recently been described to enhance memory in rodents. In this study we aimed to test whether ISRIB would reverse learning and memory deficits in the J20 mouse model of human amyloid precursor protein (hAPP) overexpression, a model that simulates many aspects of Alzheimer's disease in which memory deficits are a hallmark feature. We did not observe a significant rescue effect with ISRIB treatment on spatial learning and memory as assessed in the Morris water maze in J20 mice. We also did not observe a significant enhancement of spatial learning or memory in nontransgenic mice with ISRIB treatment, although a trend emerged for memory enhancement in one cohort of mice. Future preclinical studies with ISRIB would benefit from additional robust markers of target engagement in the brain.
authors: Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, United States; Department of Neurology, University of California -San Francisco, San Francisco, CA, United States.
authors: Erik C B
authors: EC
authors: Johnson
authors: Gladstone Institute of Neurological Disease, Gladstone Institutes , San Francisco , CA , United States.
authors: Jing
authors: J
authors: Kang
keywords: Alzheimer’s disease; ISRIB; J20 mouse model; Learning and memory