Background: Association of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice.
Scope of review: Metabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues. Mechanistic effect of insulin degrading enzyme (IDE) in decreasing blood glucose and brain Aβ levels will be elucidated. Cyclo-Z effects on these biochemical parameters will be discussed.
Major conclusion: Stimulation of IDE synthesis is effective for the clinical treatment of metabolic diseases including AD and T2D.
General significance: Cyclo-Z might be the effective treatment of AD and T2D by stimulating IDE synthesis.
Keywords: Alzheimer's Disease; Cyclo(His-Pro); Diabetes; Insulin degrading enzyme; Metabolic disease; Zinc.