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LQ12, A Novel PKC Activator, Enhances sAPP Secretion in PC-12 Cells
* , , 1 , 2
1  Drug Discovery Program, Georgetown Institute for Cognitive and Computational Science, 3970 Reservoir Road, Washington, DC 20007, USA
2  Department of Psychiatry, Biochemistry, and Neurosciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.

Abstract: Research on cellular and molecular aspects of Alzheimer’s disease over the last two decades has resulted in a significantly improved understanding of this disease. Particular achievements have occurred in the areas of molecular genetics and the biology of amyloid. This research has strengthened the notion that Ab is a central player in the disease process.1-5 Despite the progress and the data accumulated, the understanding of the pathophysiological framework remains incipient. Consequently, rational drug design targeting specific pathophysiological events or chemical entities has seen little or slow progress. Additional difficulties arise from the fact that dynamic processes are difficult to assess in the AD brain as a number of signal transduction mechanisms are altered by postmortem events.6 In addition, AD brain tissue usually becomes available after a long period of the disease, at an advanced pathological state. Therefore, significant effort has been devoted to alternative approaches.6-10 A host of cellular and molecular changes ranging from nucleic acid defects to second messenger alterations have been described in peripheral cells of AD patients.6-8,10,11 Some alterations have also been observed in neuronal animal cells and brain.12-15 Of the many alterations, PKC seems uniquely situated in the cascade of events (normal and pathological) interacting with Ab, calcium homeostasis and ion channel function. Herein we propose a framework as an initial step for drug design targeting PKC
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