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Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
AIM: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). METHODS: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large‐scale transcriptome maps provided by the Allen Human...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292638/ https://www.ncbi.nlm.nih.gov/pubmed/33955002 http://dx.doi.org/10.1111/nan.12725 |
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author | Jimenez‐Marin, Antonio Diez, Ibai Labayru, Garazi Sistiaga, Andone Caballero, Maria C. Andres‐Benito, Pol Sepulcre, Jorge Ferrer, Isidro Lopez de Munain, Adolfo Cortes, Jesus M. |
author_facet | Jimenez‐Marin, Antonio Diez, Ibai Labayru, Garazi Sistiaga, Andone Caballero, Maria C. Andres‐Benito, Pol Sepulcre, Jorge Ferrer, Isidro Lopez de Munain, Adolfo Cortes, Jesus M. |
author_sort | Jimenez‐Marin, Antonio |
collection | PubMed |
description | AIM: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). METHODS: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large‐scale transcriptome maps provided by the Allen Human Brain Atlas (AHBA). For validation, neuropathological and RNA analyses were performed in a small series of DM1 brain samples. RESULTS: Twofold: (1) From a list of preselected hypothesis‐driven genes, confirmatory analyses found that three genes play a major role in brain degeneration: dystrophin (DMD), alpha‐synuclein (SNCA) and the microtubule‐associated protein tau (MAPT). Neuropathological analyses confirmed a highly heterogeneous Tau‐pathology in DM1, different to the one in Alzheimer's disease. (2) Exploratory analyses revealed gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. RNA analyses confirmed synaptic vesicle dysfunction. CONCLUSIONS: The combination of large‐scale transcriptome interactions with brain imaging and cognitive function sheds light on the neurobiological mechanisms of brain degeneration in DM1 that might help define future therapeutic strategies and research into this condition. |
format | Online Article Text |
id | pubmed-9292638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92926382022-07-20 Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration Jimenez‐Marin, Antonio Diez, Ibai Labayru, Garazi Sistiaga, Andone Caballero, Maria C. Andres‐Benito, Pol Sepulcre, Jorge Ferrer, Isidro Lopez de Munain, Adolfo Cortes, Jesus M. Neuropathol Appl Neurobiol Original Articles AIM: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). METHODS: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large‐scale transcriptome maps provided by the Allen Human Brain Atlas (AHBA). For validation, neuropathological and RNA analyses were performed in a small series of DM1 brain samples. RESULTS: Twofold: (1) From a list of preselected hypothesis‐driven genes, confirmatory analyses found that three genes play a major role in brain degeneration: dystrophin (DMD), alpha‐synuclein (SNCA) and the microtubule‐associated protein tau (MAPT). Neuropathological analyses confirmed a highly heterogeneous Tau‐pathology in DM1, different to the one in Alzheimer's disease. (2) Exploratory analyses revealed gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. RNA analyses confirmed synaptic vesicle dysfunction. CONCLUSIONS: The combination of large‐scale transcriptome interactions with brain imaging and cognitive function sheds light on the neurobiological mechanisms of brain degeneration in DM1 that might help define future therapeutic strategies and research into this condition. John Wiley and Sons Inc. 2021-05-17 2021-12 /pmc/articles/PMC9292638/ /pubmed/33955002 http://dx.doi.org/10.1111/nan.12725 Text en © 2021 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Jimenez‐Marin, Antonio Diez, Ibai Labayru, Garazi Sistiaga, Andone Caballero, Maria C. Andres‐Benito, Pol Sepulcre, Jorge Ferrer, Isidro Lopez de Munain, Adolfo Cortes, Jesus M. Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration |
title | Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration |
title_full | Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration |
title_fullStr | Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration |
title_full_unstemmed | Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration |
title_short | Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration |
title_sort | transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type i neurodegeneration |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292638/ https://www.ncbi.nlm.nih.gov/pubmed/33955002 http://dx.doi.org/10.1111/nan.12725 |
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