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2006 Grant - Liao
sAPP and p25/CDK5 in Neurogenesis and Neuronal Death
Francesca-Fang Liao, Ph.D.
Burnham Institute for Medical Research
La Jolla, California
2006 Investigator-Initiated Research Grant
Two characteristic features of Alzheimer's disease are neurofibrillary tangles inside of nerve cells in the brain and beta-amyloid deposits in the spaces outside of nerve cells. Neurofibrillary tangles are composed of the protein tau after it becomes excessively modified by a chemical alteration called phosphorylation. The mechanisms that cause this phosphorylation are of great interest for understanding how neurofibrillary tangles form.
Francesca-Fang Liao, Ph.D., and colleagues have found evidence that the phosphorylation of tau is stimulated by beta-amyloid, the protein fragment that forms amyloid deposits. They found that an enzyme called cyclin-dependent kinase 5 (CDK5) is stimulated by beta-amyloid and appears to cause phosphorylation of tau, possibly leading to the formation of tangles.
The researchers also found a possible role for another protein called soluble amyloid precursor protein (sAPP). As its name implies, it is one of the precursors, or parent molecules, from which beta-amyloid is derived. However, Dr. Liao and colleagues found that sAPP suppresses the activation of CDK5, possibly stopping the phosphorylation of tau. They also suspect that this action may stimulate the formation of new nerve cells, even in the adult brain.
Dr. Liao and colleagues plan to continue their studies of CDK5 and its activation by beta-amyloid and suppression by sAPP. They hope that these studies will represent progress toward developing disease-modifying therapies for Alzheimer's.