Epigenetic control of the Notch and Eph signaling pathways by the prion protein Implications for prion diseases
Among the ever-growing number of self-replicating proteins involved in neurodegenerative diseases, the prion protein PrP remains the most infamous for its central role in transmissible spongiform encephalopathies (TSEs). In these diseases, pathogenic prions propagate through a seeding mechanism, where normal PrPC molecules are converted into abnormally folded scrapie isoforms termed PrPSc. Since its discovery over 30 years ago, much advance has contributed to define the host-encoded cellular prion protein PrPC as a critical relay of prion-induced neuronal cell demise. A current consensual view is that the conversion of PrPC into PrPSc in neuronal cells diverts the former from its normal function with subsequent molecular alterations affecting synaptic plasticity. Here, we report that prion infection is associated with reduced expression of key effectors of the Notch pathway in vitro and in vivo, recapitulating changes fostered by the absence of PrPC. We further show that both prion infection and PrPC depletion promote drastic alterations in the expression of a defined set of Eph receptors and their ephrin ligands, which represent important players in synaptic function. Our data indicate that defects in the Notch and Eph axes can be mitigated in response to histone deacetylase inhibition in PrPC-depleted as well as prion-infected cells. We thus conclude that infectious prions cause a loss-of-function phenotype with respect to Notch and Eph signaling and that these alterations are sustained by epigenetic mechanisms.
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Format: | artículo biblioteca |
Language: | English |
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Springer
2019
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Subjects: | Prion infection, Cellular prion protein, Notch, Eph, HDAC, |
Online Access: | http://hdl.handle.net/20.500.12792/581 http://hdl.handle.net/10261/290743 |
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dig-inia-es-10261-2907432023-02-17T12:28:57Z Epigenetic control of the Notch and Eph signaling pathways by the prion protein Implications for prion diseases Hirsch, T. Z. Martin-Lannerée, S. Reine, F. Hernandez-Rapp, J. Herzog, L. Dron, M. Privat, N. Passet, B. Halliez, S. Villa Díaz, Ana Lacroux, C. Klein, V. Haïk, S. Andréoletti, O. Torres, J. M. Vilotte, J. L. Béringue, V. Mouillet-Richard, S. Prion infection Cellular prion protein Notch Eph HDAC Among the ever-growing number of self-replicating proteins involved in neurodegenerative diseases, the prion protein PrP remains the most infamous for its central role in transmissible spongiform encephalopathies (TSEs). In these diseases, pathogenic prions propagate through a seeding mechanism, where normal PrPC molecules are converted into abnormally folded scrapie isoforms termed PrPSc. Since its discovery over 30 years ago, much advance has contributed to define the host-encoded cellular prion protein PrPC as a critical relay of prion-induced neuronal cell demise. A current consensual view is that the conversion of PrPC into PrPSc in neuronal cells diverts the former from its normal function with subsequent molecular alterations affecting synaptic plasticity. Here, we report that prion infection is associated with reduced expression of key effectors of the Notch pathway in vitro and in vivo, recapitulating changes fostered by the absence of PrPC. We further show that both prion infection and PrPC depletion promote drastic alterations in the expression of a defined set of Eph receptors and their ephrin ligands, which represent important players in synaptic function. Our data indicate that defects in the Notch and Eph axes can be mitigated in response to histone deacetylase inhibition in PrPC-depleted as well as prion-infected cells. We thus conclude that infectious prions cause a loss-of-function phenotype with respect to Notch and Eph signaling and that these alterations are sustained by epigenetic mechanisms. 2023-02-17T12:28:57Z 2023-02-17T12:28:57Z 2019 artículo Molecular Neurobiology 56: 2159-2173 (2019) 0893-7648 http://hdl.handle.net/20.500.12792/581 http://hdl.handle.net/10261/290743 10.1007/s12035-018-1193-7 1559-1182 en none Springer |
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Prion infection Cellular prion protein Notch Eph HDAC Prion infection Cellular prion protein Notch Eph HDAC |
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Prion infection Cellular prion protein Notch Eph HDAC Prion infection Cellular prion protein Notch Eph HDAC Hirsch, T. Z. Martin-Lannerée, S. Reine, F. Hernandez-Rapp, J. Herzog, L. Dron, M. Privat, N. Passet, B. Halliez, S. Villa Díaz, Ana Lacroux, C. Klein, V. Haïk, S. Andréoletti, O. Torres, J. M. Vilotte, J. L. Béringue, V. Mouillet-Richard, S. Epigenetic control of the Notch and Eph signaling pathways by the prion protein Implications for prion diseases |
description |
Among the ever-growing number of self-replicating proteins involved in neurodegenerative diseases, the prion protein PrP remains the most infamous for its central role in transmissible spongiform encephalopathies (TSEs). In these diseases, pathogenic prions propagate through a seeding mechanism, where normal PrPC molecules are converted into abnormally folded scrapie isoforms termed PrPSc. Since its discovery over 30 years ago, much advance has contributed to define the host-encoded cellular prion protein PrPC as a critical relay of prion-induced neuronal cell demise. A current consensual view is that the conversion of PrPC into PrPSc in neuronal cells diverts the former from its normal function with subsequent molecular alterations affecting synaptic plasticity. Here, we report that prion infection is associated with reduced expression of key effectors of the Notch pathway in vitro and in vivo, recapitulating changes fostered by the absence of PrPC. We further show that both prion infection and PrPC depletion promote drastic alterations in the expression of a defined set of Eph receptors and their ephrin ligands, which represent important players in synaptic function. Our data indicate that defects in the Notch and Eph axes can be mitigated in response to histone deacetylase inhibition in PrPC-depleted as well as prion-infected cells. We thus conclude that infectious prions cause a loss-of-function phenotype with respect to Notch and Eph signaling and that these alterations are sustained by epigenetic mechanisms. |
format |
artículo |
topic_facet |
Prion infection Cellular prion protein Notch Eph HDAC |
author |
Hirsch, T. Z. Martin-Lannerée, S. Reine, F. Hernandez-Rapp, J. Herzog, L. Dron, M. Privat, N. Passet, B. Halliez, S. Villa Díaz, Ana Lacroux, C. Klein, V. Haïk, S. Andréoletti, O. Torres, J. M. Vilotte, J. L. Béringue, V. Mouillet-Richard, S. |
author_facet |
Hirsch, T. Z. Martin-Lannerée, S. Reine, F. Hernandez-Rapp, J. Herzog, L. Dron, M. Privat, N. Passet, B. Halliez, S. Villa Díaz, Ana Lacroux, C. Klein, V. Haïk, S. Andréoletti, O. Torres, J. M. Vilotte, J. L. Béringue, V. Mouillet-Richard, S. |
author_sort |
Hirsch, T. Z. |
title |
Epigenetic control of the Notch and Eph signaling pathways by the prion protein Implications for prion diseases |
title_short |
Epigenetic control of the Notch and Eph signaling pathways by the prion protein Implications for prion diseases |
title_full |
Epigenetic control of the Notch and Eph signaling pathways by the prion protein Implications for prion diseases |
title_fullStr |
Epigenetic control of the Notch and Eph signaling pathways by the prion protein Implications for prion diseases |
title_full_unstemmed |
Epigenetic control of the Notch and Eph signaling pathways by the prion protein Implications for prion diseases |
title_sort |
epigenetic control of the notch and eph signaling pathways by the prion protein implications for prion diseases |
publisher |
Springer |
publishDate |
2019 |
url |
http://hdl.handle.net/20.500.12792/581 http://hdl.handle.net/10261/290743 |
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