2011 Grants - Hu

Regulation of Microglia Responses to A-Beta by Progranulin

Fenghua Hu, Ph.D.
Cornell University
Ithaca, New York

2011 New Investigator Research Grant

Brain inflammation, one of the key hallmarks of Alzheimer's disease, is caused by the abnormal activity of immune system cells called microglia. Research suggests that Alzheimer's-related microglia contain high levels of mutated progranulin, a protein that may be closely linked to both inflammation and brain degeneration. This mutated progranulin may also be a toxic factor in other brain disorders, including frontotemporal lobar degeneration. Yet scientists do not know exactly how mutated progranulin exerts its toxic effects.

For this grant, Fenghua Hu, Ph.D., and colleagues will learn more about the role of progranulin in Alzheimer's disease. The researchers will conduct several tests with microglia that have different levels of progranulin. For example, they will assess whether microglia with high progranulin levels also contain high levels of inflammation-related molecules called cytokines. The team will then analyze how progranulin levels affect the ability of microglia to break down the protein fragment beta-amyloid, a key factor in Alzheimer's. In addition, Dr. Hu's group will assess how sortilin, a protein recently found to interact with progranulin, may play a role in progranulin's toxic effects. The results of this work could shed new light on the mechanisms underlying dementia-related brain inflammation, and they could lead to novel therapies for moderating Alzheimer's disease progression.