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2016 Grants - D'Souza
Does Lenalidomide Alter Alzheimer’s Disease Neuropathologies Via Gliosis Modulation?
Gary D’Souza, Ph.D.
Arizona State University
2016 Alzheimer’s Association Research Fellowship (AARF)
Can the drug lenalidomide reduce brain inflammation and the progression of Alzheimer’s disease?
In addition to amyloid plaques and tau tangles, inflammation in the brain is a key characteristic of Alzheimer’s disease. Research suggests that excess brain inflammation may contribute to the production of beta-amyloid, the protein fragment that forms plaques. Scientists are actively exploring how links between inflammation and beta-amyloid may promote the development and progression of Alzheimer’s disease. One potential mechanism may be the abnormal activation of glial cells (gliosis) in the brain. Glial cells support the function of nerve cells, but can also release inflammatory molecules. Drugs that can safely control or dampen brain inflammation may be promising therapies to treat Alzheimer’s and other neurodegenerative diseases.
Gary D’Souza, Ph.D., and colleagues have proposed a series of experiments to determine if the drug lenalidomide may prevent brain changes associated with Alzheimer’s disease. Lenalidomide is a drug already used to treat some types of cancer. It works through several different mechanisms, including suppression of inflammation. The researchers will use a mix of glial cells and nerve cells growing in laboratory dishes to determine if lenalidomide reduces the levels of inflammatory molecules and inhibits the production of beta-amyloid. The researchers will explore which inflammatory molecules are inhibited by lenalidomide, and how this relates to the health and function of the nerve cells. Dr. D’Souza and colleagues will also administer lenalidomide to Alzheimer’s-like mice and determine if it can reduce brain inflammation, prevent the build-up of beta-amyloid and preserve learning and memory function.
This research could shed new light on links between glial cells, brain inflammation and beta-amyloid in the progression of Alzheimer’s disease. Importantly, this work could provide the foundation for determining if lenalidomide could be used to help prevent or treat Alzheimer’s disease.