Alpha 7 Nicotinic Receptors and MAP Kinase in AD Models

John Sweatt, PhD
Baylor College of Medicine (Houston, TX)
Year Awarded:
2004
Grant Duration:
April 1, 2004 to March 31, 2004
Disease:
Alzheimer's Disease
Award Amount:
$299,920
Grant Reference ID:
A2004001
Award Type:
Standard
Award Region:
US Southern

Alpha 7 Nicotinic Receptors and MAP Kinase in AD Models

Details


One of the major advances in neurobiology in the last century was the formation of the general theory that changes in synaptic connections between neurons underlie information storage in the central nervous system (CNS). By studying the mechanisms of long-lasting synaptic plasticity in model systems, researchers can generate insights into the mechanisms of learning and memory. Dr. Sweatt's past research indicates that four protein kinases play particularly prominent roles in synaptic plasticity and memory. These kinases are designated as PKA, PKC, CaMKII, and ERK MAPK. This project involves the role of the alpha7 nicotinic acetylcholine receptor in regulating these protein kinases. Alpha7 nicotinic acetylcholine receptors are abundant in the hippocampus and in cholinergic neurons from the basal forebrain, and these structures are particularly vulnerable to the ravages of Alzheimer's disease. Dr. Sweatt is now testing the hypothesis that beta-amyloid peptide directly activates the alpha7 nicotinic acetylcholine receptor and leads to the disruption of memory-related biochemical processes.

Publications

Beffert, U., Weeber, E.J., Morfini, G., Ko, J., Brady, S.T., Tsai, L.H, Sweatt, J.D., and Herz J. (2004) Reelin and cyclin-dependent kinase 5-dependent signals cooperate in regulating neuronal migration and synaptic transmission. J. Neuroscience. 24(8):1897-1906.  

Marschang, P., Brich, J., Weeber, E.J., Sweatt, J.D., Shelton, J.M., Richardson, J.A., Hammer, R. E., and Herz J. (2004) Normal development and fertility of knockout mice lacking the tumor suppressor gene LRP1b suggest functional compensation by LRP1. Mol. Cell Biol. 24(9):3782-3793.  

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