血源性胰淀粉样蛋白--阿尔茨海默病的治疗靶点

IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY
Florin Despa
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引用次数: 0

摘要

阿尔茨海默病(AD)的病理与大脑中β淀粉样蛋白(Aβ)和神经纤维tau缠结的积累有关。一个耐人寻味的问题是,针对独立于Aβ和tau病理学的因素进行治疗是否可以延缓甚至阻止神经退行性变。淀粉样蛋白是一种与胰岛素共同分泌的胰腺激素,被认为在饱腹感的中枢调节中发挥作用,并在2型糖尿病患者体内形成胰腺淀粉样蛋白。越来越多的证据表明,在散发性和早发性家族性注意力缺失症中,从胰腺分泌的淀粉样蛋白与大脑中的血管和实质Aβ协同聚集形成淀粉样蛋白。淀粉样蛋白形成的人淀粉样蛋白在AD模型大鼠胰腺中的表达会加速AD样病理变化,而基因抑制淀粉样蛋白的分泌则可防止AD的影响。因此,目前的数据表明,胰腺淀粉样蛋白形成的淀粉样蛋白在改变注意力缺失症方面发挥作用;还需要进一步的研究来检验在注意力缺失症发病早期降低循环中的淀粉样蛋白水平是否能抑制认知能力的下降。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Current Alzheimer research
Current Alzheimer research 医学-神经科学
CiteScore
4.00
自引率
4.80%
发文量
64
审稿时长
4-8 weeks
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.
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