Carmela Abraham

Payment for services (e.g., consulting fees, honoraria, paid authorship)

Discovery of probes that enhance expression of the neuroprotective protein Klotho

Project Narrative Cognitive functions, such as learning and memory, are of fundamental biological importance, and diseases that affect these functions are among the most challenging biomedical problems of our time. We recently demonstrated that elevating levels of the pleotropic protein Klotho enhances cognitive functions in mice and humans, and can prevent synaptic and cognitive impairments in a transgenic mouse model that simulates key aspects of Alzheimer's disease. We hypothesize that small molecules capable of elevating Klotho levels (?Klotho boosters?) can prevent and reverse the pathogenic effects of elevated amyloid-? (A?) levels in the AD brain and therefore, in this proposal, we will begin to test these hypotheses by first identifying the best Klotho boosters for in vivo testing in wild type mice and for future testing in animal models of AD at the preclinical level.