Amylin Pharmacology in Alzheimer’s Disease Pathogenesis and Treatment

Abstract

: The metabolic peptide hormone amylin, in concert with other metabolic peptides like insulin and leptin, has an important role in metabolic homeostasis and has been intimately linked to Alzheimer’s disease (AD). Interestingly, this pancreatic amyloid peptide is known to self-aggregate much like amyloid-beta and has been reported to be a source of pathogenesis in both Type II diabetes mellitus (T2DM) and Alzheimer’s disease. The traditional “gain of toxic function” properties assigned to amyloid proteins are however contrasted by several reports highlighting neuroprotective effects amylin and a recombinant analog, pramlintide, in the context of these two diseases. This suggests that pharmacological therapies aimed at modulating the amylin receptor may be therapeutically beneficial for AD development, as they already are for T2DMM. However, the nature of amylin receptor signaling is highly complex and not well studied in the context of CNS function. Therefore, to begin to address this pharmacological paradox in amylin research, the goal of this review is to summarize the current research on amylin signaling and CNS functions and critically address paradoxical nature of this hormone's signaling in the context of AD pathogenesis.

Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials

“…Second, amylin may enhance the clearance of amyloid-beta from the brain by promoting its uptake and transport across the BBB. Finally, amylin could possibly also bind directly to amyloid-beta and prevent its toxicity to neurons [123,124]. Pramlintide, one of the amylin analogs, has demonstrated potential neuroprotective effects in a mouse model of AD.…”