The potential role of miRNA therapies in spinal muscle atrophy

Gandhi, Gayatri; Abdullah, Saifollah; Foead, Agus Iwan; Yeo, Wendy Wai Yeng

doi:10.1016/j.jns.2021.117485

Cited by 14 publications

(12 citation statements)

References 122 publications

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“…DNAs remain a primary target for several anticancer chemotherapeutics [ 12 ] and potential antimicrobial compounds [ 13 ]. RNA molecules, such as the bacterial ribosomes or human pre-mRNA of survival of motor neuron 2 (SMN2) protein, are also known targets for a number of drugs, e.g., bacterial ribosome-targeting antibiotics [ 14 , 15 ], or risdiplam [ 16 , 17 ], respectively. Other RNAs, such as mRNAs [ 18 ] and regulatory RNAs in humans [ 19 ], riboswitches in bacteria [ 20 ], and conserved non-coding RNAs in viruses [ 21 ], are considered as promising targets for new therapeutics (for review, see [ 4 , 22 , 23 ]).…”

Section: Introductionmentioning

confidence: 99%

fingeRNAt—A novel tool for high-throughput analysis of nucleic acid-ligand interactions

et al. 2022

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Computational methods play a pivotal role in drug discovery and are widely applied in virtual screening, structure optimization, and compound activity profiling. Over the last decades, almost all the attention in medicinal chemistry has been directed to protein-ligand binding, and computational tools have been created with this target in mind. With novel discoveries of functional RNAs and their possible applications, RNAs have gained considerable attention as potential drug targets. However, the availability of bioinformatics tools for nucleic acids is limited. Here, we introduce fingeRNAt—a software tool for detecting non-covalent interactions formed in complexes of nucleic acids with ligands. The program detects nine types of interactions: (i) hydrogen and (ii) halogen bonds, (iii) cation-anion, (iv) pi-cation, (v) pi-anion, (vi) pi-stacking, (vii) inorganic ion-mediated, (viii) water-mediated, and (ix) lipophilic interactions. However, the scope of detected interactions can be easily expanded using a simple plugin system. In addition, detected interactions can be visualized using the associated PyMOL plugin, which facilitates the analysis of medium-throughput molecular complexes. Interactions are also encoded and stored as a bioinformatics-friendly Structural Interaction Fingerprint (SIFt)—a binary string where the respective bit in the fingerprint is set to 1 if a particular interaction is present and to 0 otherwise. This output format, in turn, enables high-throughput analysis of interaction data using data analysis techniques. We present applications of fingeRNAt-generated interaction fingerprints for visual and computational analysis of RNA-ligand complexes, including analysis of interactions formed in experimentally determined RNA-small molecule ligand complexes deposited in the Protein Data Bank. We propose interaction fingerprint-based similarity as an alternative measure to RMSD to recapitulate complexes with similar interactions but different folding. We present an application of interaction fingerprints for the clustering of molecular complexes. This approach can be used to group ligands that form similar binding networks and thus have similar biological properties. The fingeRNAt software is freely available at https://github.com/n-szulc/fingeRNAt.

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Section: Introductionmentioning

confidence: 99%

fingeRNAt—A novel tool for high-throughput analysis of nucleic acid-ligand interactions

et al. 2022

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“…Because most of the transcriptome did not recover normal levels on GE, including some GO pathways ( Figure S3 ), and considering the relevance of miRNAs in the pathogenic mechanism of other myopathies, 31 , 32 , 33 we hypothesized that miRNA alterations might remain after the manipulation and contribute to gene expression changes after the originating mutation has been reverted. To this end, we performed an small RNA (sRNA) sequencing and analyzed miRNAs expression.…”

Section: Resultsmentioning

confidence: 99%

CRISPR-Cas9 editing of a TNPO3 mutation in a muscle cell model of limb-girdle muscular dystrophy type D2

Poyatos-García¹,

Blázquez-Bernal²,

Selva-Giménez³

et al. 2023

Molecular Therapy - Nucleic Acids

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“…miRNAs which are the targets of circRNAs have been exploited in SMA and reports have revealed their neuroprotective abilities ( Gandhi et al, 2021 ). A number of miRNAs including miR-23a (reduced the motor neuron death, increased the motor neuron size as well as muscle fiber area), miR-375 (protects the neuron from apoptosis by inhibiting the tumour suppressor gene p53), miR-9 (crucial modulator associated with SMA severity), miR-146a (regulates crucial signaling pathways in motor neurons), miR-183 (increases the motor neurons survival and improves the motor function of mice with mutant SMN), miR-206 (role in survival endogenous mechanism), and miR-431 (rescue the motor neuron neurite length phenotype through targeting chondrolectin) have been considered as potential therapeutic ncRNAs for treating SMA ( Gandhi et al, 2021 ). These miRNAs have been implicated in autophagy as well as targets of circRNAs in separate studies which warrants further investigations of circRNAs/miRNAs/autophagy axis in SMA ( Chang et al, 2012 ; Zhang et al, 2015 ; Si et al, 2018 ; Huang et al, 2019 ; Shang et al, 2021 ; Wei et al, 2021 ).…”

Section: The Enigmatic Connection Between Circrnas Autophagy and Neur...mentioning

confidence: 99%

Brain-protective mechanisms of autophagy associated circRNAs: Kick starting self-cleaning mode in brain cells via circRNAs as a potential therapeutic approach for neurodegenerative diseases

Basri

Awan²,

Yang³

et al. 2023

Front. Mol. Neurosci.

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Altered autophagy is a hallmark of neurodegeneration but how autophagy is regulated in the brain and dysfunctional autophagy leads to neuronal death has remained cryptic. Being a key cellular waste-recycling and housekeeping system, autophagy is implicated in a range of brain disorders and altering autophagy flux could be an effective therapeutic strategy and has the potential for clinical applications down the road. Tight regulation of proteins and organelles in order to meet the needs of complex neuronal physiology suggests that there is distinct regulatory pattern of neuronal autophagy as compared to non-neuronal cells and nervous system might have its own separate regulator of autophagy. Evidence has shown that circRNAs participates in the biological processes of autophagosome assembly. The regulatory networks between circRNAs, autophagy, and neurodegeneration remains unknown and warrants further investigation. Understanding the interplay between autophagy, circRNAs and neurodegeneration requires a knowledge of the multiple steps and regulatory interactions involved in the autophagy pathway which might provide a valuable resource for the diagnosis and therapy of neurodegenerative diseases. In this review, we aimed to summarize the latest studies on the role of brain-protective mechanisms of autophagy associated circRNAs in neurodegenerative diseases (including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Spinal Muscular Atrophy, Amyotrophic Lateral Sclerosis, and Friedreich’s ataxia) and how this knowledge can be leveraged for the development of novel therapeutics against them. Autophagy stimulation might be potential one-size-fits-all therapy for neurodegenerative disease as per considerable body of evidence, therefore future research on brain-protective mechanisms of autophagy associated circRNAs will illuminate an important feature of nervous system biology and will open the door to new approaches for treating neurodegenerative diseases.

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The potential role of miRNA therapies in spinal muscle atrophy

Cited by 14 publications

References 122 publications

fingeRNAt—A novel tool for high-throughput analysis of nucleic acid-ligand interactions

fingeRNAt—A novel tool for high-throughput analysis of nucleic acid-ligand interactions

CRISPR-Cas9 editing of a TNPO3 mutation in a muscle cell model of limb-girdle muscular dystrophy type D2

Brain-protective mechanisms of autophagy associated circRNAs: Kick starting self-cleaning mode in brain cells via circRNAs as a potential therapeutic approach for neurodegenerative diseases

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