Abstract
AbstractAlzheimer's disease has recently been characterized as “diabetes of the brain” or “type 3 diabetes.” Although recent clinical trials targeting amyloid β‐protein have been unsuccessful, glucose‐insulin metabolism in the brain may provide an alternative therapeutic target. In this review, we focus on three related topics: (a) how peripheral and brain insulin resistance interact with each other; (b) brain insulin resistance as a promising therapeutic target for Alzheimer's disease and anti‐diabetic drugs as potentially effective drugs; and (c) apomorphine as a novel drug that improves neuronal insulin signaling. Although apomorphine is a dopamine receptor agonist, studies in our laboratory revealed a novel effect, promoting intracellular amyloid β degradation and improving memory function in an Alzheimer's disease mouse model. Recently, we demonstrated that apomorphine treatment improved neuronal insulin resistance and activated insulin‐degrading enzyme, a major amyloid β‐degrading enzyme. In addition, we confirmed the efficacy of apomorphine for some Alzheimer's disease patients. In this context, combined treatment involving anti‐diabetic drugs and apomorphine may provide an effective therapeutic approach for Alzheimer's disease.
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