Amylin Receptor: A Potential Therapeutic Target for Alzheimer’s Disease

• Published in: Trends in molecular medicine Vol. 23; no. 8; pp. 709 - 720
• Main Authors: Fu, Wen, Patel, Aarti, Kimura, Ryoichi, Soudy, Rania, Jhamandas, Jack H
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2017
• Subjects: AC253 peptide; Alzheimer Disease - drug therapy; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer’s disease; amylin receptor; Amyloid beta-Peptides - metabolism; amyloid-β; Animals; Humans; islet amyloid polypeptide; Mice; Mice, Transgenic; Pathology; Peptides - therapeutic use; Receptors, Islet Amyloid Polypeptide - antagonists & inhibitors; Receptors, Islet Amyloid Polypeptide - genetics; Receptors, Islet Amyloid Polypeptide - metabolism; AC253 peptide; islet amyloid polypeptide (IAPP); Amylin receptor; Alzheimer's disease; amyloid-β islet amyloid polypeptide; amyloid-β; amylin receptor; Alzheimer’s disease
• ISSN: 1471-4914; 1471-499X
• DOI: 10.1016/j.molmed.2017.06.003

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, characterized by senile plaques constituting extracellular deposits of β-amyloid (Aβ) fibrils. Since Aβ accumulation in the brain is considered an early event preceding, by decades, cognitive dysfunction, disease-modifying treatments are aimed at facilitating clearance of this protein from the brain or ameliorating its toxic effects. Recent studies have identified the amylin receptor as a capable mediator of the deleterious actions of Aβ and furthermore, administration of amylin receptor-based peptides has been shown to improve spatial memory and learning in transgenic mouse models of AD. Here, by discussing available evidence, we posit that the amylin receptor could be considered a potential therapeutic target for AD, and present the rationale for using amylin receptor antagonists to treat this debilitating condition.