Mechanistic Analysis of Age-Related Clinical Manifestations in Down Syndrome.
Mechanistic Analysis of Age-Related Clinical Manifestations in Down Syndrome.
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DOI：
10.3389/fnagi.2021.700280
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发表时间：
2021
影响因子：
4.8
通讯作者：
Yu YE
中科院分区：
文献类型：
--
作者：
Chen XQ;Xing Z;Chen QD;Salvi RJ;Zhang X;Tycko B;Mobley WC;Yu YE
唐氏综合征（Down syndrome，DS）是阿尔茨海默病（Alzheimer's disease，AD）最常见的遗传病因，是由于人类21号染色体（human chromosome 21，Hsa 21）的全部或部分三体性。它还与其他表型相关，包括独特的面部特征，心脏缺陷，生长延迟，智力残疾，免疫系统异常和听力损失。所有患有DS的成年人在40岁时表现出AD样脑病理学，包括淀粉样斑块和神经元缠结，通常在60岁时表现出痴呆。有令人信服的证据表明，增加APP基因剂量对于DS中的AD是必要的，并且这种作用的机制已经开始出现，涉及99个氨基酸的C末端APP片段（β-CTF）。Hsa 21上其他三重基因的产物可能通过改变生物衰老的总体速率来改变APP三重的影响。另一个重要的与年龄相关的DS表型是听力损失，虽然其机制尚不清楚，但我们在这里描述其特征。此外，DS中的免疫系统异常（涉及干扰素途径基因和衰老）容易发生不同的感染，并可能改变COVID-19的严重程度。所有这些考虑都表明人类21三体以年龄依赖性方式影响几种疾病。因此，了解与DS的这些临床表现相关的可能的衰老相关机制将有助于在成年中后期进行治疗干预，同时阐明衰老的基本机制。
Down syndrome (DS) is the most common genetic cause of Alzheimer’s disease (AD) due to trisomy for all or part of human chromosome 21 (Hsa21). It is also associated with other phenotypes including distinctive facial features, cardiac defects, growth delay, intellectual disability, immune system abnormalities, and hearing loss. All adults with DS demonstrate AD-like brain pathology, including amyloid plaques and neurofibrillary tangles, by age 40 and dementia typically by age 60. There is compelling evidence that increased APP gene dose is necessary for AD in DS, and the mechanism for this effect has begun to emerge, implicating the C-terminal APP fragment of 99 amino acid (β-CTF). The products of other triplicated genes on Hsa21 might act to modify the impact of APP triplication by altering the overall rate of biological aging. Another important age-related DS phenotype is hearing loss, and while its mechanism is unknown, we describe its characteristics here. Moreover, immune system abnormalities in DS, involving interferon pathway genes and aging, predispose to diverse infections and might modify the severity of COVID-19. All these considerations suggest human trisomy 21 impacts several diseases in an age-dependent manner. Thus, understanding the possible aging-related mechanisms associated with these clinical manifestations of DS will facilitate therapeutic interventions in mid-to-late adulthood, while at the same time shedding light on basic mechanisms of aging.
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影响因子：
2.5
作者：
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通讯作者：
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DOI：
10.1016/j.jbc.2021.100489
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The Journal of biological chemistry
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发表时间：
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DOI：
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发表时间：
2013-08-01
影响因子：
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作者：
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