To view an abstract, select an author from the vertical list on the left.
2014 Grants - Cai D
Development of Novel Therapies Targeted at ABeta-Clearance
Dongming Cai, M.D., Ph.D.
Icahn School of Medicine at Mount Sinai
New York, New York
2014 New Investigator Research Grant
Abeta (also known as beta-amyloid) is a protein fragment thought to play an important role in the development of Alzheimer’s disease. Beta-amyloid accumulates into amyloid plaques, one of the characteristic features of Alzheimer’s disease in the brain.
One of the earliest changes in the brain associated with Alzheimer’s disease is impairment in a system nerve cells use for clearance of beta-amyloid, known as the endosome/lysosome system. High levels of a protein known as synaptojanin1 (SNJ1) have been linked to impairments in the endosome/lysosome system, as well as to Alzheimer’s disease. Reducing the levels of SNJ1 has been shown to help facilitate beta-amyloid clearance in the brains of mice.
Dongming Cai, M.D., Ph.D., and colleagues have been studying potential drug candidates to reduce SNJ1 levels in the brain. From an initial list of about 3600 chemicals, they have identified 10 that reduce SNJ1 levels and have favorable properties for possible use as drugs. They have proposed a series of experiments to determine how these 10 chemicals affect beta-amyloid levels in the brain and cognitive function.
Dr. Cai and colleagues will begin by studying how their drug candidates affect SNJ1 levels in brain cells growing in laboratory dishes. Then the researchers will explore how the drug candidates affect beta-amyloid levels and brain function in mice that have been genetically altered to have an Alzheimer’s-like condition. These studies may help in the discovery of new drug candidates to reduce beta-amyloid and nerve cell damage associated with Alzheimer’s disease and provide a basis for moving these drug candidates to future clinical trials for Alzheimer’s.