Barman Nirmal Chandra, Khan Niuz Morshed, Islam Maidul, Nain Zulkar, Roy Rajib Kanti, Haque Anwarul, Barman Shital Kumar
Department Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, 7003, Bangladesh.
Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, 9208, Bangladesh.
Neurol Ther. 2020 Dec;9(2):419-434. doi: 10.1007/s40120-020-00218-z. Epub 2020 Oct 21.
Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative disorder characterized by cognitive deficiency and development of amyloid-β (Aβ) plaques and neurofibrillary tangles, comprising hyperphosphorylated tau. The number of patients with AD is alarmingly increasing worldwide; currently, at least 50 million people are thought to be living with AD. The mutations or alterations in amyloid-β precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes are known to be associated with the pathophysiology of AD. Effective medication for AD is still elusive and many gene-targeted clinical trials have failed to meet the expected efficiency standards. The genome editing tool clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 has been emerging as a powerful technology to correct anomalous genetic functions and is now widely applied to the study of AD. This simple yet powerful tool for editing genes showed the huge potential to correct the unwanted mutations in AD-associated genes such as APP, PSEN1, and PSEN2. So, it has opened a new door for the development of empirical AD models, diagnostic approaches, and therapeutic lines in studying the complexity of the nervous system ranging from different cell types (in vitro) to animals (in vivo). This review was undertaken to study the related mechanisms and likely applications of CRISPR-Cas9 as an effective therapeutic tool in treating AD.
阿尔茨海默病(AD)是一种慢性且不可逆的神经退行性疾病,其特征为认知缺陷以及淀粉样β蛋白(Aβ)斑块和神经原纤维缠结的形成,神经原纤维缠结由过度磷酸化的tau蛋白组成。全球范围内,AD患者数量正以惊人的速度增长;目前,据信至少有5000万人患有AD。已知淀粉样β前体蛋白(APP)、早老素1(PSEN1)或早老素2(PSEN2)基因的突变或改变与AD的病理生理学相关。治疗AD的有效药物仍然难以寻觅,许多针对基因的临床试验未能达到预期的效率标准。基因组编辑工具成簇规律间隔短回文重复序列(CRISPR)-Cas9已成为一种强大的技术,可用于纠正异常的基因功能,目前已广泛应用于AD研究。这种简单却强大的基因编辑工具显示出巨大潜力,能够纠正AD相关基因(如APP、PSEN1和PSEN2)中的有害突变。因此,它为开发经验性AD模型、诊断方法以及治疗途径打开了一扇新的大门,有助于研究从不同细胞类型(体外)到动物(体内)的神经系统复杂性。本综述旨在研究CRISPR-Cas9作为治疗AD的有效治疗工具的相关机制和可能的应用。