Amylin and its G-protein-coupled receptor: A probable pathological process and drug target for Alzheimer's disease

Neuroscience
Wei Qiao Qiu

Abstract

G-protein-coupled receptors (GPCRs) are shown to be involved in Alzheimer's disease (AD) pathogenesis. However, because GPCRs include a large family of membrane receptors, it is unclear which specific GPCR or pathway with rational ligands can become effective therapeutic targets for AD. Amylin receptor (AmR) is a GPCR that mediates several activities, such as improving glucose metabolism, relaxing cerebrovascular structure, modulating inflammatory reactions and potentially enhancing neural regeneration. Recent studies show that peripheral treatments with amylin or its clinical analog, pramlintide, reduced several components of AD pathology, including amyloid plaques, tauopathy, neuroinflammation and other components in the brain, corresponding with improved learning and memory in AD mouse models. Because amylin shares a similar secondary structure with amyloid-β peptide (Aβ), I propose that the AmR/GPCR pathway is disturbed by a large amount of Aβ in the AD brain, leading to tau phosphorylation, neuroinflammation and neuronal death in the pathological cascade. Amylin-type peptides, readily crossing the blood-brain barrier (BBB), are the rational ligands to enhance this GPCR pathway and may exhibit utility as novel therapeutic a...Continue Reading

References

Nov 28, 2012·Current Opinion in Endocrinology, Diabetes, and Obesity·Jonathan D Roth

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Citations

Mar 10, 2019·Diabetes/metabolism Research and Reviews·Xiaojing LiChenguang Du
Feb 7, 2018·Addiction Biology·Aimilia Lydia KalafateliElisabet Jerlhag
Jun 22, 2019·Expert Review of Clinical Pharmacology·Luana LionettoPaolo Martelletti
Mar 1, 2020·Scientific Reports·Youssef M MousaAmal Kaddoumi
Jul 16, 2019·Journal of Alzheimer's Disease : JAD·Qini GanWei Qiao Qiu
Apr 23, 2018·ACS Pharmacology & Translational Science·Rebekah L BowerDebbie L Hay

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