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The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease

MicroRNAs (miRNAs) are small double-stranded RNAs that exert a fine-tuning sequence-specific regulation of cell transcriptome. While one unique miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by various miRNAs that bind to complementary sequences at 3’-untranslated region...

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Autores principales: Titze-de-Almeida, Simoneide S., Soto-Sánchez, Cristina, Fernandez, Eduardo, Koprich, James B., Brotchie, Jonathan M., Titze-de-Almeida, Ricardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226753/
https://www.ncbi.nlm.nih.gov/pubmed/32244357
http://dx.doi.org/10.3390/cells9040841
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author Titze-de-Almeida, Simoneide S.
Soto-Sánchez, Cristina
Fernandez, Eduardo
Koprich, James B.
Brotchie, Jonathan M.
Titze-de-Almeida, Ricardo
author_facet Titze-de-Almeida, Simoneide S.
Soto-Sánchez, Cristina
Fernandez, Eduardo
Koprich, James B.
Brotchie, Jonathan M.
Titze-de-Almeida, Ricardo
author_sort Titze-de-Almeida, Simoneide S.
collection PubMed
description MicroRNAs (miRNAs) are small double-stranded RNAs that exert a fine-tuning sequence-specific regulation of cell transcriptome. While one unique miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by various miRNAs that bind to complementary sequences at 3’-untranslated regions for triggering the mechanism of RNA interference. Unfortunately, dysregulated miRNAs play critical roles in many disorders, including Parkinson’s disease (PD), the second most prevalent neurodegenerative disease in the world. Treatment of this slowly, progressive, and yet incurable pathology challenges neurologists. In addition to L-DOPA that restores dopaminergic transmission and ameliorate motor signs (i.e., bradykinesia, rigidity, tremors), patients commonly receive medication for mood disorders and autonomic dysfunctions. However, the effectiveness of L-DOPA declines over time, and the L-DOPA-induced dyskinesias commonly appear and become highly disabling. The discovery of more effective therapies capable of slowing disease progression –a neuroprotective agent–remains a critical need in PD. The present review focus on miRNAs as promising drug targets for PD, examining their role in underlying mechanisms of the disease, the strategies for controlling aberrant expressions, and, finally, the current technologies for translating these small molecules from bench to clinics.
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spelling pubmed-72267532020-05-18 The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease Titze-de-Almeida, Simoneide S. Soto-Sánchez, Cristina Fernandez, Eduardo Koprich, James B. Brotchie, Jonathan M. Titze-de-Almeida, Ricardo Cells Review MicroRNAs (miRNAs) are small double-stranded RNAs that exert a fine-tuning sequence-specific regulation of cell transcriptome. While one unique miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by various miRNAs that bind to complementary sequences at 3’-untranslated regions for triggering the mechanism of RNA interference. Unfortunately, dysregulated miRNAs play critical roles in many disorders, including Parkinson’s disease (PD), the second most prevalent neurodegenerative disease in the world. Treatment of this slowly, progressive, and yet incurable pathology challenges neurologists. In addition to L-DOPA that restores dopaminergic transmission and ameliorate motor signs (i.e., bradykinesia, rigidity, tremors), patients commonly receive medication for mood disorders and autonomic dysfunctions. However, the effectiveness of L-DOPA declines over time, and the L-DOPA-induced dyskinesias commonly appear and become highly disabling. The discovery of more effective therapies capable of slowing disease progression –a neuroprotective agent–remains a critical need in PD. The present review focus on miRNAs as promising drug targets for PD, examining their role in underlying mechanisms of the disease, the strategies for controlling aberrant expressions, and, finally, the current technologies for translating these small molecules from bench to clinics. MDPI 2020-03-31 /pmc/articles/PMC7226753/ /pubmed/32244357 http://dx.doi.org/10.3390/cells9040841 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Titze-de-Almeida, Simoneide S.
Soto-Sánchez, Cristina
Fernandez, Eduardo
Koprich, James B.
Brotchie, Jonathan M.
Titze-de-Almeida, Ricardo
The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease
title The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease
title_full The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease
title_fullStr The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease
title_full_unstemmed The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease
title_short The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease
title_sort promise and challenges of developing mirna-based therapeutics for parkinson’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226753/
https://www.ncbi.nlm.nih.gov/pubmed/32244357
http://dx.doi.org/10.3390/cells9040841
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