Tripathi Siddhant, Sharma Yashika, Kumar Dileep
Department of Pharm. Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India.
Department of Pharm. Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India.
Protein Pept Lett. 2024;31(11):862-883. doi: 10.2174/0109298665335550241011080252.
Despite significant research efforts, Alzheimer's disease (AD), the primary cause of dementia in older adults worldwide, remains a neurological challenge for which there are currently no effective therapies. There are substantial financial, medical, and personal costs associated with this condition.Important pathological features of AD include hyperphosphorylated microtubule-associated protein Tau, the formation of amyloid β (Aβ) peptides from amyloid precursor protein (APP), and continuous inflammation that ultimately results in neuronal death. Important histological markers of AD, amyloid plaques, and neurofibrillary tangles are created when Aβ and hyperphosphorylated Tau build-up. Nevertheless, a thorough knowledge of the molecular players in AD pathophysiology is still elusive. Recent studies have shown how noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate gene expression at the transcriptional and posttranscriptional levels in a variety of diseases, including AD. There is increasing evidence to support the involvement of these ncRNAs in the genesis and progression of AD, making them promising as biomarkers and therapeutic targets. As a result, therapeutic approaches that target regulatory ncRNAs are becoming more popular as potential means of preventing the progression of AD. This review explores the posttranscriptional relationships between ncRNAs and the main AD pathways, highlighting the potential of ncRNAs to advance AD treatment. In AD, ncRNAs, especially miRNAs, change expression and present potential targets for therapy. MiR-346 raises Aβ through APP messenger Ribonucleic Acid (mRNA), whereas miR-107 may decrease Aβ by targeting beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). They are promising early AD biomarkers due to their stability in cerebrospinal fluid (CSF) and blood. Furthermore, additional research is necessary to determine the role that RNA fragments present in AD-related protein deposits play in AD pathogenesis.
尽管进行了大量研究工作,但阿尔茨海默病(AD)作为全球老年人痴呆症的主要病因,仍然是一项神经学挑战,目前尚无有效的治疗方法。这种疾病会带来巨大的经济、医疗和个人成本。AD的重要病理特征包括微管相关蛋白Tau的过度磷酸化、淀粉样前体蛋白(APP)形成淀粉样β(Aβ)肽以及最终导致神经元死亡的持续炎症。当Aβ和过度磷酸化的Tau积累时,就会形成AD的重要组织学标志物——淀粉样斑块和神经原纤维缠结。然而,对于AD病理生理学中分子参与者的全面了解仍然难以捉摸。最近的研究表明,包括微小RNA(miRNA)、长链非编码RNA(lncRNA)和环状RNA(circRNA)在内的非编码RNA(ncRNA)如何在包括AD在内的多种疾病的转录和转录后水平上调节基因表达。越来越多的证据支持这些ncRNA参与AD的发生和发展,这使得它们有望成为生物标志物和治疗靶点。因此,以调节性ncRNA为靶点的治疗方法作为预防AD进展的潜在手段正变得越来越流行。本综述探讨了ncRNA与主要AD途径之间的转录后关系,强调了ncRNA在推进AD治疗方面的潜力。在AD中,ncRNA,尤其是miRNA,会改变表达并呈现出潜在的治疗靶点。MiR-346通过APP信使核糖核酸(mRNA)提高Aβ水平,而miR-107可能通过靶向β-位点淀粉样前体蛋白裂解酶1(BACE1)来降低Aβ水平。由于它们在脑脊液(CSF)和血液中的稳定性,它们有望成为早期AD生物标志物。此外,还需要进一步研究以确定AD相关蛋白沉积物中存在的RNA片段在AD发病机制中所起的作用。