Effects of DHA and EGCG on the alpha-secretase mediated processing of APP




Azizi, Hawmid

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University of Guelph


Therapeutic strategies currently used for Alzheimer's disease (AD) are ineffective at stopping disease progression and result in side effects which may further degrade the quality of life for those suffering with the debilitating disease. Until more promising drugs are developed and tested, finding ways to reduce the risk of disease and development may be more practical. This thesis explores the effects of two dietary modulators, docosahexaenoic acid (DHA) and epigallocatechin gallate (EGCG) on the α-secretase-mediated processing of amyloid precursor protein (APP). Using an SH-SY5Y human neuroblastoma cell-line model, DHA and EGCG showed increases on the mRNA and protein expression of the putative α-secretases, ADAM9, ADAM10, and ADAM17. Combining lower doses of DHA and EGCG showed increases that were similar to the highest doses of DHA and EGCG alone. This thesis also presents, some mechanisms by which DHA and EGCG in combination increase the expression of ADAM10, the physiologically relevant α-secretase.



dietary modulators, docosahexaenoic acid, epigallocatechin gallate, α-secretase-mediated processing, amyloid precursor protein