{"title":"血源性胰淀粉样蛋白--阿尔茨海默病的治疗靶点","authors":"Florin Despa","doi":"10.2174/1567205020666230217091540","DOIUrl":null,"url":null,"abstract":"<p><p>Alzheimer Disease (AD) pathology has been linked to brain accumulation of β amyloid (Aβ) and neurofibrillary tau tangles. An intriguing question is whether targeting therapeutically factors independent of Aβ and tau pathologies could delay or even stop neurodegeneration. Amylin, a pancreatic hormone co-secreted with insulin, is believed to play a role in the central regulation of satiation and was shown to form pancreatic amyloid in persons with type-2 diabetes mellitus. Accumulating evidence demonstrates that amyloid-forming amylin secreted from the pancreas synergistically aggregates with vascular and parenchymal Aβ in the brain, in both sporadic and early-onset familial AD. Pancreatic expression of amyloid-forming human amylin in AD-model rats accelerates AD-like pathology, whereas genetically suppressed amylin secretion protects against AD effects. Thus, current data suggest a role of pancreatic amyloid-forming amylin in modifying AD; further research is required to test whether lowering circulating amylin levels early during AD pathogenesis may curb cognitive decline.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bloodborne Pancreatic Amylin, A Therapeutic Target for Alzheimer's Disease.\",\"authors\":\"Florin Despa\",\"doi\":\"10.2174/1567205020666230217091540\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Alzheimer Disease (AD) pathology has been linked to brain accumulation of β amyloid (Aβ) and neurofibrillary tau tangles. An intriguing question is whether targeting therapeutically factors independent of Aβ and tau pathologies could delay or even stop neurodegeneration. Amylin, a pancreatic hormone co-secreted with insulin, is believed to play a role in the central regulation of satiation and was shown to form pancreatic amyloid in persons with type-2 diabetes mellitus. Accumulating evidence demonstrates that amyloid-forming amylin secreted from the pancreas synergistically aggregates with vascular and parenchymal Aβ in the brain, in both sporadic and early-onset familial AD. Pancreatic expression of amyloid-forming human amylin in AD-model rats accelerates AD-like pathology, whereas genetically suppressed amylin secretion protects against AD effects. Thus, current data suggest a role of pancreatic amyloid-forming amylin in modifying AD; further research is required to test whether lowering circulating amylin levels early during AD pathogenesis may curb cognitive decline.</p>\",\"PeriodicalId\":10810,\"journal\":{\"name\":\"Current Alzheimer research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2023-02-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Alzheimer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1567205020666230217091540\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Alzheimer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1567205020666230217091540","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Bloodborne Pancreatic Amylin, A Therapeutic Target for Alzheimer's Disease.
Alzheimer Disease (AD) pathology has been linked to brain accumulation of β amyloid (Aβ) and neurofibrillary tau tangles. An intriguing question is whether targeting therapeutically factors independent of Aβ and tau pathologies could delay or even stop neurodegeneration. Amylin, a pancreatic hormone co-secreted with insulin, is believed to play a role in the central regulation of satiation and was shown to form pancreatic amyloid in persons with type-2 diabetes mellitus. Accumulating evidence demonstrates that amyloid-forming amylin secreted from the pancreas synergistically aggregates with vascular and parenchymal Aβ in the brain, in both sporadic and early-onset familial AD. Pancreatic expression of amyloid-forming human amylin in AD-model rats accelerates AD-like pathology, whereas genetically suppressed amylin secretion protects against AD effects. Thus, current data suggest a role of pancreatic amyloid-forming amylin in modifying AD; further research is required to test whether lowering circulating amylin levels early during AD pathogenesis may curb cognitive decline.
期刊介绍:
Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.