Role of Amylin and its Receptors in Neurodegeneration

Amylin (islet amyloid polypeptide) and amyloid beta protein (A beta), identified as proteinaceous deposits within the pancreas of diabetics and the brain of Alzheimer's patients respectively, share many biophysical, physiological and neurotoxic properties. Although no specific "A beta receptor" has been identified, emerging evidence suggests that the amylin receptor serves a putative target receptor for the actions of A beta in the brain. The amylin receptor consists of a calcitonin receptor dimerized with receptor activity-modifying proteins and is widely distributed within central nervous system. A beta can directly activate this G protein-coupled receptor and trigger multiple intracellular signal transduction messengers and pathways that include calcium, cAMP, ERK1/2 and Fos. Growing evidence suggests that amylin and amylin receptors are involved in many aspects of neurodegenerative pathophysiology. Developing therapeutic strategies aimed at modulating amylin receptor function may prove useful for treatment of neurodegenerative diseases such as Alzheimer's disease.