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An analysis of components of the EGFR/ MAP kinase pathway in the regulation of APP processing
Abstract   Peer reviewed

An analysis of components of the EGFR/ MAP kinase pathway in the regulation of APP processing

Daniel R. Marenda and Aleister J. Saunders
Alzheimer's & dementia, v 4(4S Part 7), pp T222-T222
Jul 2008
DOI: https://doi.org/10.1016/j.jalz.2008.05.642

Abstract

Background A central process in the pathogenesis of Alzheimer's Disease (AD) is the generation and deposition of the Amyloid β (Aβ) peptide in AD patient brains. Aβ is a major component of amyloid plaques, and is generated through the intra-membrane proteolysis of the Amyloid Precursor Protein (APP). One of the proteases essential to the generation of Aβ is γ-secretase. Thus, a deeper understanding of the endogenous factors that regulate γ-secretase activity, and of how those factors specifically control γ-secretase function, will likely be significant to our understanding of the mechanisms that contribute to AD pathogenesis. It has been previously reported that the MAP Kinase pathway is a key negative regulator of γ-secretase activity, and thus APP metabolism, though the specific mechanism for this regulation is not fully understood. Methods To better understand the specific contributions of the various components of the MAP Kinase pathway in γ-secretase function and APP metabolism, we have used an established model of γ-secretase in the developing Drosophila eye. We have examined the effect of genetic disruption of MAP Kinase pathway components on the phenotype of this AD model. Results We report here that the subcellular localization of MAP Kinase, and regulation of the expression of the MAP Kinase transcription factor Pointed (Elk-1) are important for γ-secretase activity in this AD model. Conclusions Our results suggest that the subcellular localization of MAP Kinase, and those factors that regulate this localization, are important for APP processing, and may therefore be significant in AD pathogenesis.

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