A pancreatic player in dementia:pathological role for islet amyloid polypeptide accumulation in the brain  

作　　者：Angelina S.Bortoletto Ronald J.Parchem 

机构地区：[1]Center for Cell and Gene Therapy,Stem Cell and Regenerative Medicine Center,Department of Neuroscience,Department of Molecular and Cellular Biology,Translational Biology and Molecular Medicine Program,Medical Scientist Training Program,Baylor College of Medicine,Houston,TX,USA

出　　处：《Neural Regeneration Research》2023年第10期2141-2146,共6页中国神经再生研究（英文版）

基　　金：supported by The Mike Hogg Fund;Baylor College of Medicine Medical Scientist Training Program,NICHD R01HD099252(to RJP)and R01HD098131(to RJP);the NHLBI T32 HL092332(to ASB)。

摘　　要：Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.

关 键 词：Alzheimer’s disease AMYLIN AMYLOID DEMENTIA diabetes human islet amyloid polypeptide islet amyloid polypeptide PROTOFIBRILS type 2 diabetes mellitus vascular dementia 

分 类 号：R741[医药卫生—神经病学与精神病学]