Current progress on <scp>microRNAs</scp>‐based therapeutics in neurodegenerative diseases

Pereira, Patrícia; Queiroz, João A.; Figueiras, Ana; Sousa, Fani

doi:10.1002/wrna.1409

Cited by 30 publications

(29 citation statements)

References 132 publications

(270 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29). These miR-NAs are small non-coding regulatory RNAs, initially transcribed as long primary miRNA transcripts (pri-miRNA) containing a double- stranded hairpin structure.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

“…Multiple proteins can associate with the miRNA–Ago–mRNA complex, determining the type of regulation to be carried out by the miRNA, with mRNA degradation being one of the possibilities (reviewed in refs. 29,30). Synthetic oligonucleotides imitating ds-miRNAs can enter the miRNA processing pathway as miRNA mimics and guide the regulation of their target mRNA.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

See 1 more Smart Citation

Oligonucleotide therapies for disorders of the nervous system

2017

View full text Add to dashboard Cite

Oligonucleotide therapies are currently experiencing a resurgence driven by advances in backbone chemistry and discoveries of novel therapeutic pathways that can be uniquely and efficiently modulated by the oligonucleotide drugs. A quarter of a century has passed since oligonucleotides were first applied in living mammalian brain to modulate gene expression. Despite challenges in delivery to the brain, multiple oligonucleotide-based compounds are now being developed for treatment of human brain disorders by direct delivery inside the blood brain barrier (BBB). Notably, the first new central nervous system (CNS)-targeted oligonucleotide-based drug (nusinersen/Spinraza) was approved by US Food and Drug Administration (FDA) in late 2016 and several other compounds are in advanced clinical trials. Human testing of brain-targeted oligonucleotides has highlighted unusual pharmacokinetic and pharmacodynamic properties of these compounds, including complex active uptake mechanisms, low systemic exposure, extremely long half-lives, accumulation and gradual release from subcellular depots. Further work on oligonucleotide uptake, development of formulations for delivery across the BBB and relevant disease biology studies are required for further optimization of the oligonucleotide drug development process for brain applications.

show abstract

“…29). These miR-NAs are small non-coding regulatory RNAs, initially transcribed as long primary miRNA transcripts (pri-miRNA) containing a double- stranded hairpin structure.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Section: Mechanisms Of Actionmentioning

confidence: 99%

Oligonucleotide therapies for disorders of the nervous system

2017

View full text Add to dashboard Cite

show abstract

“…Data indicate that miRNAs are expressed in a temporally and spatially controlled manner within the brain and are also well‐known contributors to synaptic plasticity, neuronal differentiation, and development . MicroRNAs also play a major role in immune functioning, hematopoiesis, proliferation, neurodegenerative disorders, embryonic development, and in‐born errors of metabolism . miRNAs have been utilized as therapeutic targets, as they are reported to act as biomarkers for several diseases .…”

Section: Types Of Ncrnasmentioning

confidence: 99%

Noncoding RNAs in ischemic stroke: time to translate

Kaur

Sarmah

Saraf

et al. 2018

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Stroke is devastating and a major cause of morbidity and mortality around globe. Current interventions for ischemic stroke include thrombolytics, clot retrieval devices and/or intravenous tissue plasminogen activators (tPA), the latter two becoming the first line of treatment. Owing to the limitations of tPA to elicit therapeutic benefits in a narrow time window, new pharmacological interventions are needed. Exploring noncoding RNAs (ncRNAs) may be a promising option for stroke treatment. ncRNAs are endogenous molecules that play key roles in the pathophysiology of many functions and diseases, including during ischemic stroke. Small ncRNAs such as microRNAs, Piwi-interacting RNAs, and long ncRNAs affect the genetic machinery at molecular levels. These small ncRNAs, along with their target genes and RNA transcripts, are involved in repair and recovery mechanisms after stroke. The potential of ncRNAs to regulate physiological processes highlights their potential therapeutic importance. Here, we enumerate the details and roles of different types of ncRNAs as biomarkers and targets for future stroke intervention.

show abstract

“…Until now, 18 clinical trials involving neurodegenerative diseases and miRNAs have been documented in the database of the National Institute of Health based in the USA ( ), which strongly suggests the high potential for miRNAs to be used as biopharmaceuticals or as biomarkers, respectively, in the treatment or diagnosis of neurodegenerative disorders [ 14 , 17 ]. However, the manufacturing (production, recovery, and purification) and delivery of miRNAs into the brain poses many technical challenges, which need to be addressed if the application of these molecules in pre-clinical and clinical trials is envisaged [ 18 ]. Recently, our research group proposed an innovative strategy that allows the biosynthesis and purification of recombinant pre-miR-29b to decrease the BACE1 and endogenous Aβ peptides expression levels [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Brain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine Polyplexes

et al. 2020

Self Cite

View full text Add to dashboard Cite

The efficacy of brain therapeutics is largely hampered by the presence of the blood–brain barrier (BBB), mainly due to the failure of most (bio) pharmaceuticals to cross it. Accordingly, this study aims to develop nanocarriers for targeted delivery of recombinant precursor microRNA (pre-miR-29b), foreseeing a decrease in the expression of the BACE1 protein, with potential implications in Alzheimer’s disease (AD) treatment. Stearic acid (SA) and lactoferrin (Lf) were successfully exploited as brain-targeting ligands to modify cationic polymers (chitosan (CS) or polyethyleneimine (PEI)), and its BBB penetration behavior was evaluated. The intracellular uptake of the dual-targeting drug delivery systems by neuronal cell models, as well as the gene silencing efficiency of recombinant pre-miR-29b, was analyzed in vitro. Labeled pre-miR-29b-CS/PEI-SA-Lf systems showed very strong fluorescence in the cytoplasm and nucleus of RBE4 cells, being verified the delivery of pre-miR-29b to neuronal cells after 1 h transfection. The experiment of transport across the BBB showed that CS-SA-Lf delivered 65% of recombinant pre-miR-29b in a period of 4 h, a significantly higher transport ratio than the 42% found for PEI-SA-Lf in the same time frame. Overall, a novel procedure for the dual targeting of DDS is disclosed, opening new perspectives in nanomedicines delivery, whereby a novel drug delivery system harvests the merits and properties of the different immobilized ligands.

show abstract

Current progress on microRNAs‐based therapeutics in neurodegenerative diseases

Cited by 30 publications

References 132 publications

Oligonucleotide therapies for disorders of the nervous system

Oligonucleotide therapies for disorders of the nervous system

Noncoding RNAs in ischemic stroke: time to translate

Brain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine Polyplexes

Contact Info

Product

Resources

About