Cargando…

The Current Challenges for Drug Discovery in CNS Remyelination

The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneratio...

Descripción completa

Detalles Bibliográficos
Autores principales: Balestri, Sonia, Del Giovane, Alice, Sposato, Carola, Ferrarelli, Marta, Ragnini-Wilson, Antonella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001072/
https://www.ncbi.nlm.nih.gov/pubmed/33809224
http://dx.doi.org/10.3390/ijms22062891
_version_ 1783671144418639872
author Balestri, Sonia
Del Giovane, Alice
Sposato, Carola
Ferrarelli, Marta
Ragnini-Wilson, Antonella
author_facet Balestri, Sonia
Del Giovane, Alice
Sposato, Carola
Ferrarelli, Marta
Ragnini-Wilson, Antonella
author_sort Balestri, Sonia
collection PubMed
description The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient’s lives by delaying or even preventing neurodegeneration. Drugs promoting CNS remyelination in animal models have been identified recently, mostly as a result of repurposing phenotypical screening campaigns that used novel oligodendrocyte cellular models. Although none of these have as yet arrived in the clinic, promising candidates are on the way. Many questions remain. Among the most relevant is the question if there is a time window when remyelination drugs should be administrated and why adult remyelination fails in many neurodegenerative pathologies. Moreover, a significant challenge in the field is how to reconstitute the oligodendrocyte/axon interaction environment representative of healthy as well as disease microenvironments in drug screening campaigns, so that drugs can be screened in the most appropriate disease-relevant conditions. Here we will provide an overview of how the field of in vitro models developed over recent years and recent biological findings about how oligodendrocytes mature after reactivation of their staminal niche. These data have posed novel questions and opened new views about how the adult brain is repaired after myelin injury and we will discuss how these new findings might change future drug screening campaigns for CNS regenerative drugs.
format Online
Article
Text
id pubmed-8001072
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80010722021-03-28 The Current Challenges for Drug Discovery in CNS Remyelination Balestri, Sonia Del Giovane, Alice Sposato, Carola Ferrarelli, Marta Ragnini-Wilson, Antonella Int J Mol Sci Review The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient’s lives by delaying or even preventing neurodegeneration. Drugs promoting CNS remyelination in animal models have been identified recently, mostly as a result of repurposing phenotypical screening campaigns that used novel oligodendrocyte cellular models. Although none of these have as yet arrived in the clinic, promising candidates are on the way. Many questions remain. Among the most relevant is the question if there is a time window when remyelination drugs should be administrated and why adult remyelination fails in many neurodegenerative pathologies. Moreover, a significant challenge in the field is how to reconstitute the oligodendrocyte/axon interaction environment representative of healthy as well as disease microenvironments in drug screening campaigns, so that drugs can be screened in the most appropriate disease-relevant conditions. Here we will provide an overview of how the field of in vitro models developed over recent years and recent biological findings about how oligodendrocytes mature after reactivation of their staminal niche. These data have posed novel questions and opened new views about how the adult brain is repaired after myelin injury and we will discuss how these new findings might change future drug screening campaigns for CNS regenerative drugs. MDPI 2021-03-12 /pmc/articles/PMC8001072/ /pubmed/33809224 http://dx.doi.org/10.3390/ijms22062891 Text en © 2021 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
Balestri, Sonia
Del Giovane, Alice
Sposato, Carola
Ferrarelli, Marta
Ragnini-Wilson, Antonella
The Current Challenges for Drug Discovery in CNS Remyelination
title The Current Challenges for Drug Discovery in CNS Remyelination
title_full The Current Challenges for Drug Discovery in CNS Remyelination
title_fullStr The Current Challenges for Drug Discovery in CNS Remyelination
title_full_unstemmed The Current Challenges for Drug Discovery in CNS Remyelination
title_short The Current Challenges for Drug Discovery in CNS Remyelination
title_sort current challenges for drug discovery in cns remyelination
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001072/
https://www.ncbi.nlm.nih.gov/pubmed/33809224
http://dx.doi.org/10.3390/ijms22062891
work_keys_str_mv AT balestrisonia thecurrentchallengesfordrugdiscoveryincnsremyelination
AT delgiovanealice thecurrentchallengesfordrugdiscoveryincnsremyelination
AT sposatocarola thecurrentchallengesfordrugdiscoveryincnsremyelination
AT ferrarellimarta thecurrentchallengesfordrugdiscoveryincnsremyelination
AT ragniniwilsonantonella thecurrentchallengesfordrugdiscoveryincnsremyelination
AT balestrisonia currentchallengesfordrugdiscoveryincnsremyelination
AT delgiovanealice currentchallengesfordrugdiscoveryincnsremyelination
AT sposatocarola currentchallengesfordrugdiscoveryincnsremyelination
AT ferrarellimarta currentchallengesfordrugdiscoveryincnsremyelination
AT ragniniwilsonantonella currentchallengesfordrugdiscoveryincnsremyelination