The Latest Articles on RNA in Neurodegenerative Diseases

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on RNA in Neurodegenerative Diseases

Title: Identification of significant differentially expressed miRNA and their targets common in idiopathic Parkinson's diseaseand Parkinson plus syndrome
Authors: Neha Srivastava, Nishant Kumar Rana, Gyaneshwer Chaubey, Bhupendra Kumar, Abhishek Pathak, Vijaya Nath Mishra
Type: Research Article
Abstract:
Idiopathic Parkinson's disease is the most prevalent type of Parkinsonism. Its pathogenesis involves oxidative stress, glutamate excitotoxicity, protein aggregation, and neurodegeneration. Parkinson's plus syndrome presents additional progressing symptoms and shows temporary or no evident responses to dopaminergic therapy, whereas idiopathic Parkinson's responds effectively. Currently, there are no widely accepted biomarkers for both types of Parkinsonism. This study aims to identify differentially expressed (DE) miRNAs that target genes associated with neurodegeneration in idiopathic Parkinson's disease and Parkinson's plus syndrome by using micro RNA expression profiling and bioinformatics tools. Combined study results through miRNA expression analysis and network analysis revealed five significant miRNAs (hsa-miR-34, hsa-miR-29, hsa-miR-128, hsa-miR-3175, and hsa-miR-6809) that were found to be common in both conditions. Their selected target genes (SNCA, PAK1, and PRKN) play crucial roles in the Parkinson's disease pathway and neurodegeneration. Thus, this research sheds light on potential therapeutic targets and a common pathway between idiopathic Parkinson's disease and Parkinson's plus syndrome.
Access this article: https://doi.org/10.1016/j.humgen.2023.201253

Title: Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Parkinson’s disease
Authors: Osama A. Mohammed, Mohammed S. Elballal, Ahmed A. El-Husseiny, Emad Gamil Khidr, Manar Mohammed El Tabaa, Ola Elazazy, Mai A. Abd-Elmawla, Ahmed E. Elesawy, Henwa M. Ibrahim, Ahmed I. Abulsoud, Walaa A. El-Dakroury, Sherif S. Abdel Mageed, Mahmoud A. Elrebehy, Yousra Nomier, Mustafa Ahmed Abdel-Reheim, Hussein M. El-Husseiny, Abdulla M.A. Mahmoud, Sameh Saber, Ahmed S. Doghish
Type: Review Article
Abstract:
Parkinson's disease (PD) is a debilitating neurological disorder characterized by the impairment of the motor system, resulting in symptoms such as resting tremor, cogwheel rigidity, bradykinesia, difficulty with gait, and postural instability. The occurrence of striatal dopamine insufficiency can be attributed to a notable decline in dopaminergic neurons inside the substantia nigra pars compacta. Additionally, the development of Lewy bodies serves as a pathological hallmark of PD. While current therapy approaches for PD aim to preserve dopaminergic neurons or replenish dopamine levels in the brain, it is important to acknowledge that achieving complete remission of the condition remains elusive. MicroRNAs (miRNAs, miR) are a class of small, non-coding ribonucleic acids involved in regulating gene expression at the post-transcriptional level. The miRNAs play a crucial part in the underlying pathogenic mechanisms of several neurodegenerative illnesses, including PD. The aim of this review is to explore the role of miRNAs in regulating genes associated with the onset and progression of PD, investigate the potential of miRNAs as a diagnostic tool, assess the effectiveness of targeting specific miRNAs as an alternative therapeutic strategy to impede disease advancement, and discuss the utilization of newly developed nanoparticles for delivering miRNAs as neurodegenerative therapies.
Access this article: https://doi.org/10.1016/j.prp.2023.155023

Title: Mechanisms of microRNA-132 in central neurodegenerative diseases: A comprehensive review
Authors: Chenxi Mu, Meng Gao, Weijing Xu, Xun Sun, Tianhao Chen, Hui Xu, Hongbin Qiu
Type: Review
Abstract:
MicroRNA-132 (miR-132) is a highly conserved molecule that plays a crucial regulatory role in central nervous system (CNS) disorders. The expression levels of miR-132 exhibit variability in various neurological disorders and have been closely linked to disease onset and progression. The expression level of miR-132 in the CNS is regulated by a diverse range of stimuli and signaling pathways, including neuronal migration and integration, dendritic outgrowth, and complexity, synaptogenesis, synaptic plasticity, as well as inflammation and apoptosis activation. The aberrant expression of miR-132 in various central neurodegenerative diseases has garnered widespread attention. Clinical studies have revealed altered miR-132 expression levels in both chronic and acute CNS diseases, positioning miR-132 as a potential biomarker or therapeutic target. An in-depth exploration of miR-132 holds the promise of enhancing our understanding of the mechanisms underlying CNS diseases, thereby offering novel insights and strategies for disease diagnosis and treatment. It is anticipated that this review will assist researchers in recognizing the potential value of miR-132 and in generating innovative ideas for clinical trials related to CNS degenerative diseases.
Access this article: https://doi.org/10.1016/j.biopha.2023.116029

Title: Recommendations for detection, validation, and evaluation of RNA editing events in cardiovascular and neurological/neurodegenerative diseases
Authors: Korina Karagianni, Alessia Bibi, Alisia Madé, Shubhra Acharya, Mikko Parkkonen, Teodora Barbalata, Prashant K. Srivastava, David de Gonzalo-Calvo, Constanza Emanueli, Fabio Martelli, Yvan Devaux, Dimitra Dafou, A. Yaël Nossent
Type: Review
Abstract:
RNA editing, a common and potentially highly functional form of RNA modification, encompasses two different RNA modifications, namely adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U) editing. As inosines are interpreted as guanosines by the cellular machinery, both A-to-I and C-to-U editing change the nucleotide sequence of the RNA. Editing events in coding sequences have the potential to change the amino acid sequence of proteins, whereas editing events in noncoding RNAs can, for example, affect microRNA target binding. With advancing RNA sequencing technology, more RNA editing events are being discovered, studied, and reported. However, RNA editing events are still often overlooked or discarded as sequence read quality defects. With this position paper, we aim to provide guidelines and recommendations for the detection, validation, and follow-up experiments to study RNA editing, taking examples from the fields of cardiovascular and brain disease. We discuss all steps, from sample collection, storage, and preparation, to different strategies for RNA sequencing and editing-sensitive data analysis strategies, to validation and follow-up experiments, as well as potential pitfalls and gaps in the available technologies. This paper may be used as an experimental guideline for RNA editing studies in any disease context.
Access this article: https://doi.org/10.1016/j.omtn.2023.102085

Title: METTL3-mediated m6A RNA methylation was involved in aluminum-induced neurotoxicity
Authors: Lingling Yang, Liping Chen, Wenxue Li, Yan Zhang, Guangyu Yang, Bing Huang, Yufang Cen, Huiqi Wang, Xueqin Yang, Fangqin Lin, Yaqin Pan, Guangzi Qi
Type: Research Article
Abstract:
Aluminum (Al) exposure has been linked to the development of a variety of neurodegenerative diseases. However, whether m6A RNA methylation participated in Al-induced neurotoxicity remain to be defined. In this study, mice were administrated with aluminum-lactate at dose of 220 mg/kg. bw by gavage for 3 months. Meanwhile, the primary hippocampal neurons were isolated and treated with 0, 50, 100, 150 μM aluminum-lactate, respectively for 7 days. Al exposure caused neuronal shrinkage, decreased Nissl bodies, and increased apoptosis. In accordance, in vitro studies also showed that Al exposure led to neuronal apoptosis in a dose-dependent manner, together with the decline in m6A RNA methylation levels. Moreover, the mRNA expression of Mettl3, Mettl14, Fto, and Ythdf2 were decreased upon Al exposure. Notably, the protein expression of METTL3 was dramatically down-regulated by 42% and 35% in Al-treated mice and neurons, suggesting METTL3 might exert a crucial role in Al-induced neurotoxicity. We next established a mouse model with hippocampus-specific overexpressing of Mettl3 gene to confirm the regulatory role of RNA methylation and found that METTL3 overexpression relieved the neurological injury induced by Al. The integrated MeRIP-seq and RNA-seq analysis elucidated that 631 genes were differentially expressed at both m6A RNA methylation and mRNA expression. Notably, EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, protein digestion and absorption might be involved in Al-induced neurotoxicity. Moreover, VEGFA, Thbs1, and PDGFB might be the central molecules. Collectively, our findings provide the novel sight into the role of m6A RNA methylation in neurodegenerative disease induced by Al.
Access this article: https://doi.org/10.1016/j.ecoenv.2023.115878