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Title: Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration
Author: Jiménez Marín, Antonio
Diez, Ibai
Labayru, Garazi
Sistiaga, Andone
Caballero, Maria C.
Andrés Benito, Pol
Sepulcre, Jorge
Ferrer, Isidro (Ferrer Abizanda)
López de Munain, Adolfo
Cortés, Jesús M.
Keywords: Malalties neurodegeneratives
Neurodegenerative Diseases
Issue Date: 17-May-2021
Publisher: Wiley
Abstract: 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.
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It is part of: Neuropathology and Applied Neurobiology, 2021
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Neurociències (UBNeuro))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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