当前位置: X-MOL 学术Mini-Rev. Med. Chem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A Systematic Review of Current Progresses in The Nucleic Acid-Based Therapies for Neurodegeneration with Implications for Alzheimer's disease.
Mini-Reviews in Medicinal Chemistry ( IF 3.8 ) Pub Date : 2020-08-31 , DOI: 10.2174/1389557520666200513122357
Maryam Ghaffari 1 , Nima Sanadgol 1 , Mohammad Abdollahi 2
Affiliation  

Recently, manipulation of gene expression and switching genes on or off highlight the potential of nucleic acid-based therapies (NA-BTs). Alzheimer’s Disease (AD) is a common devastating neurodegenerative disease (NDs) responsible for 60-80% of all cases of dementia and predicted as a main public health concern among aged populations. The aim of this study was to outline the current research in the field of NA-BTs for the treatment of AD disabilities, including strategies to suppress the memory and learning defects, to promote recovery processes, and to reinforce social relationships in these patients. This review was performed via evaluating PubMed reported studies from January 2010 to November 2019. Also, reference lists were checked to find additional studies. All intermediation or complementarity of animal models, case-control and cohort studies, and controlled trials (CTs) on specific NA-BTs to AD were acceptable, although in vitro studies were excluded due to the considerable diversities and heterogeneities. After removing the duplicates according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) instruction, we merged remaining titles across search databases. There are 48 ongoing studies related to the application of nucleic acids in the treatment and diagnosis of AD where more consideration is given to DNA targeting strategies (18 targets for vectors and aptamers), antisense oligonucleotides (10 targets), micro-RNAs mimics (7 targets), antagomiRs (6 targets), small interferences-RNAs (5 targets), as well as mRNAs (2 targets) respectively. All of these targets are grouped into 4 categories according to their role in molecular pathways where amyloid-β (18 targets), neural survival (11 targets), memory and cognition (8 targets), and tau (3 targets) are more targeted pathways, respectively. With recent successes in the systemic delivery of nucleic acids via intravenous injection; it is worth investing in the production of new-generation medicines. There are still several challenges for NA-BTs including, their delivery to the effective modulators, mass production at low cost, sustaining efficacy and minimizing off‐target effects. Regarding miRNA-based therapies, given the obvious involvement of miRNAs in numerous facets of brain disease, and the many sophisticated techniques for delivery to the brain, miRNA-based therapies will make new hope for the treatment of neurological diseases such as AD.



中文翻译:

对以核酸为基础的神经退行性疾病治疗的最新进展的系统综述,对阿尔茨海默氏病有影响。

最近,基因表达的操纵和基因的开启或关闭突出了基于核酸的疗法(NA-BT)的潜力。阿尔茨海默氏病(AD)是一种常见的毁灭性神经退行性疾病(NDs),占所有痴呆病例的60-80%,预计是老年人口中的主要公共健康问题。这项研究的目的是概述在NA-BTs治疗AD残疾领域的当前研究,包括抑制记忆和学习缺陷,促进康复过程以及加强这些患者的社会关系的策略。通过评估2010年1月至2019年11月PubMed报告的研究进行了该评价。此外,还检查了参考文献清单以查找其他研究。动物模型的所有中介或互补性,病例对照和队列研究以及针对AD的特定NA-BT的对照试验(CT)是可以接受的,尽管由于相当多的多样性和异质性而排除了体外研究。根据系统分析和荟萃分析(PRISMA)指令的首选报告项删除了重复项后,我们在搜索数据库中合并了其余标题。正在进行48项与核酸在AD的治疗和诊断中的应用相关的研究,其中更多地考虑了DNA靶向策略(载体和适体的18个靶标),反义寡核苷酸(10个靶标),micro-RNA模拟物(7个靶标),antagomiRs(6个靶标),小干扰RNA(5个靶标)和mRNA(2个靶标)。根据它们在分子途径中的作用,将所有这些靶标分为4类,其中淀粉样β(18个靶标),神经存活(11个靶标),记忆和认知(8个靶标)和tau(3个靶标)是更有针对性的途径。 , 分别。在通过静脉内注射全身性递送核酸方面取得了近期成功;值得投资生产新一代药物。NA-BT仍然面临一些挑战,包括将其交付给有效的调节剂,以低成本大量生产,维持疗效并最大程度地降低脱靶效应。关于基于miRNA的疗法,鉴于miRNA明显参与了脑部疾病的众多方面,并且采用了许多复杂的技术可将其递送至大脑,

更新日期:2020-10-19
down
wechat
bug