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2019 Alzheimer's Association Research Grant (AARG)

Nup153 as target to improve neurogenesis and cognitive function in AD

Can stem cells that reside in the brain be activated to help replace nerve cells that are lost in early-stage Alzheimer’s disease?

Claudia Colussi, Ph.D.
CNR-Institute of Cell Biology and Neurobiology
Rome, Italy


Past studies indicate that the loss of nerve cells in the hippocampus, a brain region that is vital for learning and memory, occurs early in Alzheimer’s disease. This loss of nerve cell is caused by both damage to the cells and impairment of a process called “neurogenesis”—the creation of new nerve cells by neural stem cells. These neural stem cells are immature cells —found exclusively in adult hippocampus— that can develop into any kind of brain cell, given certain signals. Previous studies found that a protein called Nup153 promotes neurogenesis in these cells. Preliminary results from Dr. Claudia Colussi’s study show that in genetically engineered Alzheimer’s-like mice, the Nup153 protein does not function properly and these mice are unable to create new nerve cells from their neural stem cells.

Research Plan

Dr. Colussi and colleagues will determine whether restoring Nup153 function in genetically engineered Alzheimer’s-like mice will promote neurogenesis in neural stem cells. The researchers will also investigate whether restoring Nup153 functionality improves learning and memory in these mice. Additionally, Dr. Colussi plans to use special type of stem cells from adult tissue called induced Pluripotent Stem Cells (iPSCs) that will be collected from volunteers with and without Alzheimer’s disease. iPSCs can be reprogrammed to grow into any cell type in the human body. The researchers will monitor the ability of iPSCs to grow into neural stem cells in a laboratory dish and test whether exposure to Nup153 enables them to create new nerve cells.  


An understanding of how Nup153 is involved in the creation of new nerve cells in the brain may lead to the development of new treatments that promote neurogenesis to replace lost nerve cells and slow the progression of Alzheimer’s disease.

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