A review of glucoregulatory hormones potentially applicable to the treatment of Alzheimer's disease: mechanism and brain delivery

Abstract

Background Despite the accumulating research efforts, the current treatment of Alzheimer's disease (AD) remains far from achieving any clinical success in modifying the underlying pathological conditions. Area covered Therefore, it is an imminent task to discover more potent anti-AD drugs, as well as deepen the understanding of the disease mechanism. A group of potential drug candidates for the AD may be the hormones that involve in the glucose homeostasis and lipid metabolism, as the type 2 diabetes mellitus (T2DM) and obesity have been recognized as major risk factors of the AD. Expert opinion Indeed, up to date, many researches have reported the potential therapeutic effects of the glucoregulatory hormones, such as GLP-1, adipokines (adiponectin, leptin), and ghrelin. However, despite their anti-AD activity, there remains a bottleneck challenge for their successful delivery to the brain. In the present review, we provide an overview of the therapeutic potentials of glucoregulatory hormones and their receptor agonists for the AD. In the latter part, we also discuss the delivery strategies across the blood brain barrier, with a particular focus on previous studies that used the Trojan horse technology.