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自闭症和阿尔茨海默病在症状、遗传和机制上存在重叠。

Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer's Disease.

机构信息

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

出版信息

Biomolecules. 2021 Nov 4;11(11):1635. doi: 10.3390/biom11111635.

Abstract

Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders affecting two opposite ends of life span, i.e., childhood and old age. Both disorders pose a cumulative threat to human health, with the rate of incidences increasing considerably worldwide. In the context of recent developments, we aimed to review correlated symptoms and genetics, and overlapping aspects in the mechanisms of the pathogenesis of ASD and AD. Dementia, insomnia, and weak neuromuscular interaction, as well as communicative and cognitive impairments, are shared symptoms. A number of genes and proteins linked with both disorders have been tabulated, including MECP2, ADNP, SCN2A, NLGN, SHANK, PTEN, RELN, and FMR1. Theories about the role of neuron development, processing, connectivity, and levels of neurotransmitters in both disorders have been discussed. Based on the recent literature, the roles of FMRP (Fragile X mental retardation protein), hnRNPC (heterogeneous ribonucleoprotein-C), IRP (Iron regulatory proteins), miRNAs (MicroRNAs), and α-, β0, and γ-secretases in the posttranscriptional regulation of cellular synthesis and processing of APP (amyloid-β precursor protein) have been elaborated to describe the parallel and overlapping routes and mechanisms of ASD and AD pathogenesis. However, the interactive role of genetic and environmental factors, oxidative and metal ion stress, mutations in the associated genes, and alterations in the related cellular pathways in the development of ASD and AD needs further investigation.

摘要

自闭症谱系障碍 (ASD) 和阿尔茨海默病 (AD) 是影响生命跨度两端的神经发育和神经退行性疾病,即儿童期和老年期。这两种疾病都对人类健康构成累积威胁,全球发病率显著增加。在最近的发展背景下,我们旨在综述 ASD 和 AD 相关症状和遗传学,并探讨其发病机制中的重叠方面。痴呆、失眠和弱神经肌肉相互作用以及沟通和认知障碍是共同的症状。许多与这两种疾病相关的基因和蛋白质已被列出,包括 MECP2、ADNP、SCN2A、NLGN、SHANK、PTEN、RELN 和 FMR1。关于神经元发育、加工、连接和神经递质水平在这两种疾病中的作用的理论也已被讨论。基于最近的文献,FMRP(脆性 X 智力低下蛋白)、hnRNPC(异质核糖核蛋白-C)、IRP(铁调节蛋白)、miRNAs(MicroRNAs)和 α、β0 和 γ-分泌酶在 APP(淀粉样β前体蛋白)的细胞合成和加工的转录后调控中的作用已被详细阐述,以描述 ASD 和 AD 发病机制的平行和重叠途径和机制。然而,遗传和环境因素、氧化和金属离子应激、相关基因的突变以及相关细胞途径的改变在 ASD 和 AD 发展中的交互作用仍需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b24/8615882/5868dcea0436/biomolecules-11-01635-g001.jpg

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