Alzheimer Disease-Associated Mutations in Protein Kinase C

2018-2019

The research supported by Cure Alzheimer’s Fund has shown that a key protein that is turned off in cancer is excessively active in Alzheimer’s disease. This protein, called protein kinase C, is an information processor, or “signal transducer,” that regulates cellular activities. Its activity needs to be exactly balanced to maintain normal cellular function. Reduced function promotes cell survival, a hallmark of cancer. Analysis of genetic mutations identified in the Genes to TherapiesÔprogram by Rudolph Tanzi, Ph.D., revealed that mutations found in some patients with Alzheimer’s disease actually enhance the function of protein kinase C. When this mutation is introduced into mice, they have behavioral deficits associated with Alzheimer’s disease. This work identifies protein kinase C as a promising therapeutic target in Alzheimer’s disease.

2014-2017

This proposal addresses whether a key protein that is turned off in cancer, a disease characterized by uncontrolled cellular growth and survival, is excessively active in Alzheimer’s disease, a degenerative disease. This protein, called protein kinase C, is an information processor, or “signal transducer,” that regulates cellular activities. Its activity needs to be precisely balanced to maintain normal cellular function. Reduced function promotes cell survival, a hallmark of cancer. Analysis of genetic mutations identified in the Genes to Therapies™ program by Rudy Tanzi reveals that mutations found in some patients with Alzheimer’s disease enhance the function of protein kinase C. This project examines whether enhanced signaling by protein kinase C generally is associated with the pathology of Alzheimer’s disease, identifying protein kinase C as a promising therapeutic target.