2014-2015 Alzheimer’s and Related Diseases Research Award*

Neuroprotection and Alzheimer’s Disease

VCoA*The Virginia Center on Aging which administers the Alzheimer’s and Related Diseases Research Award Fund for the Commonwealth of Virginia, provides seed money to researchers in Virginia to stimulate innovative research into biomedical and psychosocial aspects of dementia, including cell biology, caregiving, and animal modeling.


Neuroprotection and Alzheimer’s Disease

Robin Couch, PhD

George Mason University

A radically different therapeutic approach for the treatment of Alzheimer’s disease, known as neuroprotection, involves the use of therapeutic agents to defend nerve cells from death. One of the best neuroprotection agents is nerve growth factor (NGF), a protein that is naturally produced in the brain. Nerve growth factor not only prevents cognitive decline, it also delays the progression of Alzheimer’s disease by keeping the neurons alive. However, because it can’t enter into the brain from the bloodstream, nerve growth factor therapy requires direct administration to the brain. To circumvent this problem, this research group has identified protein kinase C (PKC) and several of its specific downstream cell signaling partners as promising targets for drug-induced upregulation of NGF secretion.  They will further this investigation by using a series of protein specific agonists and antagonists to validate select members of the PKC signal transduction pathway, thereby highlighting them as promising targets for the development of therapeutics.

(Dr. Couch may be contacted at 703/993-4770, rcouch@gmu.edu )

REPORT:

Nerve growth factor (NGF), a protein naturally produced in the brain, is capable of preventing neuronal cell death, such as that associated with Alzheimer’s disease (AD).  Recent preclinical and clinical AD studies have noted a reduction in the rate of cognitive decline upon treatment with NGF. However, because NGF is unable to penetrate the blood brain barrier, current means of delivering NGF directly to the brain are highly invasive and cost prohibitive. Oral drugs capable of stimulating the upregulation of NGF in the brain are preferred. To that end, this research group has identified protein kinase C (PKC) and several of its downstream effectors as critical to the upregulation of NGF protein. They used a series of protein specific agonists and antagonists to validate select members of the PKC signal transduction pathway, thereby highlighting them as promising targets for the development of new therapeutics for the treatment of AD.

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