Department of Zoology, School of Biological Sciences, Central University of Punjab, Ghudda 151 401, Bathinda, Punjab, India.
Department of Biochemistry and Molecular Biology, Guru Nanak Dev University, Amritsar, 143101, Punjab, India.
Mol Neurobiol. 2022 Oct;59(10):6107-6124. doi: 10.1007/s12035-022-02950-z. Epub 2022 Jul 22.
Alzheimer's disease (AD) is a progressive degeneration of neurons due to the accumulation of amyloid-β peptide (Aβ) and hyper-phosphorylation of tau protein in the neuronal milieu leading to increased oxidative stress and apoptosis. Numerous factors contribute towards the progression of AD, including miRNA, which are 22-24 nucleotides long sequence which acts as critical regulators of cellular processes by binding to 3' UTR of mRNA, regulating its expression post-transcriptionally. This review aims to determine the miRNA with the most significant dysregulation in the brain and cerebrospinal fluid (CSF) of human patients. A systemized inclusion/exclusion criterion has been utilized based on selected keywords followed by screening of those articles to conclude a list of 8 highly dysregulated miRNAs based on the fold change of AD vs control patients, which could be used in clinical testing as these miRNAs play central role in the pathophysiology of AD. Furthermore, a network study of highly dysregulated miRNA estimated the association of these miRNA in the mediation of Aβ generation and aggregation, inhibition of autophagy, reduction of Aβ clearance, microglial and astrocytic activation, neuro-inflammation, tau hyper-phosphorylation, and synaptic loss.
阿尔茨海默病（AD）是由于神经元环境中淀粉样β肽（Aβ）的积累和 tau 蛋白的过度磷酸化导致神经元退化，导致氧化应激和细胞凋亡增加。许多因素导致 AD 的进展，包括 miRNA，其长度为 22-24 个核苷酸，通过与 mRNA 的 3'UTR 结合，作为细胞过程的关键调节剂，在转录后调节其表达。本综述旨在确定大脑和人类患者脑脊液（CSF）中失调最严重的 miRNA。根据选定的关键词利用系统的纳入/排除标准，然后筛选这些文章，得出了 8 个高度失调的 miRNA 列表，这些 miRNA 的失调倍数与 AD 患者与对照患者相比，可用于临床测试，因为这些 miRNA 在 AD 的病理生理学中发挥核心作用。此外，对高度失调 miRNA 的网络研究估计了这些 miRNA 在介导 Aβ生成和聚集、抑制自噬、减少 Aβ清除、小胶质细胞和星形胶质细胞激活、神经炎症、tau 过度磷酸化和突触丢失中的作用。
