Current Status of microRNA-Based Therapeutic Approaches in Neurodegenerative Disorders

Paul, Sujay; Bravo-Vázquez, Luis Alberto; Uribe, Samantha Pérez; Reyes-Pérez, Paula; Sharma, Ashutosh

doi:10.3390/cells9071698

Cited by 79 publications

(54 citation statements)

References 148 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, another current challenge is the delivery of the therapeutic agent to the desired location in the human body. In addition to viral vectors, liposomes and nanoparticles, the use of exosomes for these purposes has been increasingly considered [ 262 ], since the transport of miRNAs is one of their key roles in long-distance intercellular communication. Even though miRNA research in vitro and in animal models of AD suggest the potential of certain miRNAs in AD therapy, this is still a relatively new direction in AD research.…”

Section: Treatment Opportunities Through Epigeneticsmentioning

confidence: 99%

Epigenetics of Alzheimer’s Disease

et al. 2021

View full text Add to dashboard Cite

There are currently no validated biomarkers which can be used to accurately diagnose Alzheimer’s disease (AD) or to distinguish it from other dementia-causing neuropathologies. Moreover, to date, only symptomatic treatments exist for this progressive neurodegenerative disorder. In the search for new, more reliable biomarkers and potential therapeutic options, epigenetic modifications have emerged as important players in the pathogenesis of AD. The aim of the article was to provide a brief overview of the current knowledge regarding the role of epigenetics (including mitoepigenetics) in AD, and the possibility of applying these advances for future AD therapy. Extensive research has suggested an important role of DNA methylation and hydroxymethylation, histone posttranslational modifications, and non-coding RNA regulation (with the emphasis on microRNAs) in the course and development of AD. Recent studies also indicated mitochondrial DNA (mtDNA) as an interesting biomarker of AD, since dysfunctions in the mitochondria and lower mtDNA copy number have been associated with AD pathophysiology. The current evidence suggests that epigenetic changes can be successfully detected, not only in the central nervous system, but also in the cerebrospinal fluid and on the periphery, contributing further to their potential as both biomarkers and therapeutic targets in AD.

show abstract

Section: Treatment Opportunities Through Epigeneticsmentioning

confidence: 99%

Epigenetics of Alzheimer’s Disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…While GWAS approaches follow an unbiased strategy, targeted association studies have the advantage to provide an improved statistical power while focusing on genetic variants or genes for which further information on possible disease-related aspects are available. To this end, one category of promising genes are microRNAs (miRNAs), which are considered excellent disease biomarkers [ 4 ] and even encouraging therapeutic targets [ 5 , 6 ], specifically for complex diseases. MiRNAs are small post-transcriptional regulators by incorporating into the RNA-induced silencing complex (RISC), which binds to mRNA transcripts in the cytosol and contributes to their degradation or translational repression [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic Locus 15q24.1 Reveals a Gender-Specific Association with Neovascular but Not Atrophic Age-Related Macular Degeneration (AMD)

Kiel

Strunz

Graßmann

et al. 2020

Cells

View full text Add to dashboard Cite

Genome-wide association studies (GWAS) have identified an abundance of genetic loci associated with complex traits and diseases. In contrast, in-depth characterization of an individual genetic signal is rarely available. Here, we focus on the genetic variant rs2168518 in 15q24.1 previously associated with age-related macular degeneration (AMD), but only with suggestive evidence. In a two-step procedure, we initially conducted a series of association analyses to further delineate the association of rs2168518 with AMD but also with other complex phenotypes by using large independent datasets from the International AMD Genomics Consortium (IAMDGC) and the UK Biobank. We then performed a functional annotation with reference to gene expression regulation based on data from the Genotype-Tissue Expression (GTEx) project and RegulomeDB. Association analysis revealed a gender-specific association with male AMD patients and an association predominantly with choroidal neovascularization. Further, the AMD association colocalizes with an association signal of several blood pressure-related phenotypes and with the gene expression regulation of CYP1A1, a member of the cytochrome P450 superfamily of monooxygenases. Functional annotation revealed altered transcription factor (TF) binding sites for gender-specific TFs, including SOX9 and SRY. In conclusion, the pleiotropic 15q24.1 association signal suggests a shared mechanism between blood pressure regulation and choroidal neovascularization with a potential involvement of CYP1A1.

show abstract

“…Another RNA based gene therapy strategy is the use of miRNAs that bind and inhibit complementary mRNA targets [ 85 ]. The inappropriate expression of miRNA has been linked to a variety of diseases, and there have been many studies utilizing miRNA to treat neurodegenerative diseases [ 86 ]. However, unlike mRNA therapy, miRNA have not reached a critical milestone in clinical use, and its safety and efficacy needs to be ensured as overexpression has caused organ failure and death in rats [ 85 , 87 ].…”

Section: Discussionmentioning

confidence: 99%

Use of Gene Therapy in Retinal Ganglion Cell Neuroprotection: Current Concepts and Future Directions

Rhee

Shih

2021

Biomolecules

View full text Add to dashboard Cite

We systematically reviewed published translational research on gene-based therapy for retinal ganglion cell (RGC) neuroprotection. A search was conducted on Entrez PubMed on 23 December 2020 using the keywords “gene therapy”, “retinal ganglion cell” and “neuroprotection. The initial search yielded 82 relevant articles. After restricting publications to those with full text available and in the English language, and then curating for only original articles on gene-based therapy, the final yield was 18 relevant articles. From the 18 papers, 17 of the papers utilized an adeno-associated viral (AAV) vector for gene therapy encoding specific genes of interest. Specifically, six of the studies utilized an AAV vector encoding brain-derived neurotrophic factor (BDNF), two of the studies utilized an AAV vector encoding erythropoietin (EPO), the remaining 10 papers utilized AAV vectors encoding different genes and one microRNA study. Although the literature shows promising results in both in vivo and in vitro models, there is still a significant way to go before gene-based therapy for RGC neuroprotection can proceed to clinical trials. Namely, the models of injury in many of the studies were more acute in nature, unlike the more progressive and neurodegenerative pathophysiology of diseases, such as glaucoma. The regulation of gene expression is also highly unexplored despite the use of AAV vectors in the majority of the studies reviewed. It is also expected that with the successful launch of messenger ribonucleic acid (mRNA)-based vaccinations in 2020, we will see a shift towards this technology for gene-based therapy in glaucoma neuroprotection.

show abstract

Current Status of microRNA-Based Therapeutic Approaches in Neurodegenerative Disorders

Cited by 79 publications

References 148 publications

Epigenetics of Alzheimer’s Disease

Epigenetics of Alzheimer’s Disease

Pleiotropic Locus 15q24.1 Reveals a Gender-Specific Association with Neovascular but Not Atrophic Age-Related Macular Degeneration (AMD)

Use of Gene Therapy in Retinal Ganglion Cell Neuroprotection: Current Concepts and Future Directions

Contact Info

Product

Resources

About