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Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases
In vivo cell reprogramming of glial cells offers a promising way to generate new neurons in the adult mammalian nervous system. This approach might compensate for neuronal loss occurring in neurological disorders, but clinically viable tools are needed to advance this strategy from bench to bedside....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962309/ https://www.ncbi.nlm.nih.gov/pubmed/35203608 http://dx.doi.org/10.3390/biomedicines10020399 |
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author | Contardo, Matilde De Gioia, Roberta Gagliardi, Delia Comi, Giacomo Pietro Ottoboni, Linda Nizzardo, Monica Corti, Stefania |
author_facet | Contardo, Matilde De Gioia, Roberta Gagliardi, Delia Comi, Giacomo Pietro Ottoboni, Linda Nizzardo, Monica Corti, Stefania |
author_sort | Contardo, Matilde |
collection | PubMed |
description | In vivo cell reprogramming of glial cells offers a promising way to generate new neurons in the adult mammalian nervous system. This approach might compensate for neuronal loss occurring in neurological disorders, but clinically viable tools are needed to advance this strategy from bench to bedside. Recently published work has described the successful neuronal conversion of glial cells through the repression of a single gene, polypyrimidine tract-binding protein 1 (Ptbp1), which encodes a key RNA-binding protein. Newly converted neurons not only express correct markers but they also functionally integrate into endogenous brain circuits and modify disease symptoms in in vivo models of neurodegenerative diseases. However, doubts about the nature of “converted” neurons, in particular in vivo, have been raised, based on concerns about tracking reporter genes in converted cells. More robust lineage tracing is needed to draw definitive conclusions about the reliability of this strategy. In vivo reprogramming and the possibility of implementing it with approaches that could be translated into the clinic with antisense oligonucleotides targeting a single gene like Ptbp1 are hot topics. They warrant further investigation with stringent methods and criteria of evaluation for the ultimate treatment of neurological diseases. |
format | Online Article Text |
id | pubmed-8962309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89623092022-03-30 Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases Contardo, Matilde De Gioia, Roberta Gagliardi, Delia Comi, Giacomo Pietro Ottoboni, Linda Nizzardo, Monica Corti, Stefania Biomedicines Review In vivo cell reprogramming of glial cells offers a promising way to generate new neurons in the adult mammalian nervous system. This approach might compensate for neuronal loss occurring in neurological disorders, but clinically viable tools are needed to advance this strategy from bench to bedside. Recently published work has described the successful neuronal conversion of glial cells through the repression of a single gene, polypyrimidine tract-binding protein 1 (Ptbp1), which encodes a key RNA-binding protein. Newly converted neurons not only express correct markers but they also functionally integrate into endogenous brain circuits and modify disease symptoms in in vivo models of neurodegenerative diseases. However, doubts about the nature of “converted” neurons, in particular in vivo, have been raised, based on concerns about tracking reporter genes in converted cells. More robust lineage tracing is needed to draw definitive conclusions about the reliability of this strategy. In vivo reprogramming and the possibility of implementing it with approaches that could be translated into the clinic with antisense oligonucleotides targeting a single gene like Ptbp1 are hot topics. They warrant further investigation with stringent methods and criteria of evaluation for the ultimate treatment of neurological diseases. MDPI 2022-02-07 /pmc/articles/PMC8962309/ /pubmed/35203608 http://dx.doi.org/10.3390/biomedicines10020399 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Contardo, Matilde De Gioia, Roberta Gagliardi, Delia Comi, Giacomo Pietro Ottoboni, Linda Nizzardo, Monica Corti, Stefania Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases |
title | Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases |
title_full | Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases |
title_fullStr | Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases |
title_full_unstemmed | Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases |
title_short | Targeting PTB for Glia-to-Neuron Reprogramming In Vitro and In Vivo for Therapeutic Development in Neurological Diseases |
title_sort | targeting ptb for glia-to-neuron reprogramming in vitro and in vivo for therapeutic development in neurological diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962309/ https://www.ncbi.nlm.nih.gov/pubmed/35203608 http://dx.doi.org/10.3390/biomedicines10020399 |
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