An amylin analog
Pramlintide is a non-amyloidogenic analog of the antidiabetic peptide hormone amylin that contains proline residues substituted at positions 25, 28, and 29.1 It stimulates cAMP production in HEK293 cells expressing human amylin receptor 1a (AMY1a), AMY2a, and AMY3a (EC50s = 0.35, 22.9, and 0.89 nM, respectively).2 Pramlintide inhibits human islet amyloid polypeptide fibrilization in a concentration-dependent manner.3 In vivo, pramlintide (200 pg/kg) reduces brain levels of amyloid-β (1-40) and increases spontaneous alternation in the Y-maze in the Tg2576 transgenic mouse model of Alzheimer's disease.4
1.Wang, H., Abedini, A., Ruzsicska, B., et al.Rationally designed, nontoxic, nonamyloidogenic analogues of human islet amyloid polypeptide with improved solubilityBiochemistry53(37)5876-5584(2014) 2.Gingell, J.J., Burns, E.R., and Hay, D.L.Activity of pramlintide, rat and human amylin but not Aβ1-42 at human amylin receptorsEndocrinology155(1)21-26(2014) 3.Wang, H., Ridgway, Z., Cao, P., et al.Analysis of the ability of pramlintide to inhibit amyloid formation by human islet amyloid polypeptide reveals a balance between optimal recognition and reduced amyloidogenicityBiochemistry54(44)6704-6711(2015) 4.Zhu, H., Wang, X., Wallack, M., et al.Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's diseaseMol. Psychiatry20(2)252-262(2015)
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