Research Project: Neuron Senescence as Mediator of Neurodegeneration in Alzheimer’s disease
The CART Fund will award Claudio Torres, Ph.D., Drexel University College of Medicine, a 2017 research grant in the amount of $50,000. The grant will be awarded on May 9, 2017 at the Annual Meeting of The CART Fund in Columbia, SC.
Summary of Research Project:
Alzheimer’s Disease (AD) currently affects about 5.4 million Americans and currently has no cure. Aging is the greatest risk factor for AD; however, the mechanisms of aging that predispose the brain to the development of the disease are still largely unknown.
Cellular senescence is a hallmark of aging that may influence AD. Senescent cells are irreversibly growth arrested, resistant to apoptosis and they release a complex mixture of factors that profoundly affects neighboring cells and tissues by creating a pro-inflammatory microenvironment. Our previous research has shown for the first time that the brain of AD patients is significantly populated with senescent astrocytes, which have a loss in brain-specific genes and a gain of genes associated with inflammation, suggesting that the presence of senescent cells in the AD brain may have profound consequences on brain function.
Our recent evidence demonstrates the presence of senescent neurons in the brain of AD patients. Cellular senescence has previously been associated with dividing cells and senescence of non-dividing cells, like neurons, is an understudied area. Our central hypothesis is that AD is accompanied by an increase in the population of senescent neurons, which due to their resistance to apoptosis, can persist, leading to neuron dysfunction and neurodegeneration. We propose the following specific aims: 1) Perform a comprehensive analysis of the senescence program in neurons in the AD brain. 2) Determine changes in gene expression in neurons during progression to AD. 3) Evaluate the effects of rapamycin on paracrine- and Aβ induced neuron senescence and neurodegeneration.
The Coins for Alzheimer’s Research Trust Fund (CART) is a project of the Rotary Clubs of North America. Founded in 1995 in Sumter SC, CART provides financial support for Alzheimer’s research projects that are yet to be supported by extensive preliminary data but have the potential to substantially advance biomedical research. Learn more at www.cartfund.org