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Honors Theses

Andrews University

Alzheimer's Disease

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Design And Synthesis Of A Novel Lsoxazoline As A Potential Pam-Agonist, Josselyn Roosenberg Apr 2019

Design And Synthesis Of A Novel Lsoxazoline As A Potential Pam-Agonist, Josselyn Roosenberg

Honors Theses

Progression of Alzheimer's disease is associated with a loss of Ml receptor activation in the brain. However, a lack of clinical success following attempts to activate the Ml receptor at the orthosteric site has contributed to a transition towards the allosteric pocket of the receptor. Here, positive allosteric modulators (PAMs) interact to potentiate the acetylcholine response. Recent research proposes that optimization of PAM activity at the expense of intrinsic agonism may posit a means to limit adverse side effects. Therefore, this project proposes a design and synthesis of a novel isoxazoline as a potent PAM agent with weak intrinsic agonism.