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Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease

Learning and memory and the underlying cellular correlate, long-term synaptic plasticity, involve regulation by posttranslational modifications (PTMs). Here we demonstrate that conjugation with the small ubiquitin-like modifier (SUMO) is a novel PTM required for normal synaptic and cognitive functio...

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Autores principales: Lee, Linda, Dale, Elena, Staniszewski, Agnes, Zhang, Hong, Saeed, Faisal, Sakurai, Mikako, Fa', Mauro, Orozco, Ian, Michelassi, Francesco, Akpan, Nsikan, Lehrer, Helena, Arancio, Ottavio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250909/
https://www.ncbi.nlm.nih.gov/pubmed/25448527
http://dx.doi.org/10.1038/srep07190
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author Lee, Linda
Dale, Elena
Staniszewski, Agnes
Zhang, Hong
Saeed, Faisal
Sakurai, Mikako
Fa', Mauro
Orozco, Ian
Michelassi, Francesco
Akpan, Nsikan
Lehrer, Helena
Arancio, Ottavio
author_facet Lee, Linda
Dale, Elena
Staniszewski, Agnes
Zhang, Hong
Saeed, Faisal
Sakurai, Mikako
Fa', Mauro
Orozco, Ian
Michelassi, Francesco
Akpan, Nsikan
Lehrer, Helena
Arancio, Ottavio
author_sort Lee, Linda
collection PubMed
description Learning and memory and the underlying cellular correlate, long-term synaptic plasticity, involve regulation by posttranslational modifications (PTMs). Here we demonstrate that conjugation with the small ubiquitin-like modifier (SUMO) is a novel PTM required for normal synaptic and cognitive functioning. Acute inhibition of SUMOylation impairs long-term potentiation (LTP) and hippocampal-dependent learning. Since Alzheimer's disease (AD) prominently features both synaptic and PTM dysregulation, we investigated SUMOylation under pathology induced by amyloid-β (Aβ), a primary neurotoxic molecule implicated in AD. We observed that SUMOylation is dysregulated in both human AD brain tissue and the Tg2576 transgenic AD mouse model. While neuronal activation normally induced upregulation of SUMOylation, this effect was impaired by Aβ(42) oligomers. However, supplementing SUMOylation via transduction of its conjugating enzyme, Ubc9, rescued Aβ-induced deficits in LTP and hippocampal-dependent learning and memory. Our data establish SUMO as a novel regulator of LTP and hippocampal-dependent cognition and additionally implicate SUMOylation impairments in AD pathogenesis.
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spelling pubmed-42509092014-12-08 Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease Lee, Linda Dale, Elena Staniszewski, Agnes Zhang, Hong Saeed, Faisal Sakurai, Mikako Fa', Mauro Orozco, Ian Michelassi, Francesco Akpan, Nsikan Lehrer, Helena Arancio, Ottavio Sci Rep Article Learning and memory and the underlying cellular correlate, long-term synaptic plasticity, involve regulation by posttranslational modifications (PTMs). Here we demonstrate that conjugation with the small ubiquitin-like modifier (SUMO) is a novel PTM required for normal synaptic and cognitive functioning. Acute inhibition of SUMOylation impairs long-term potentiation (LTP) and hippocampal-dependent learning. Since Alzheimer's disease (AD) prominently features both synaptic and PTM dysregulation, we investigated SUMOylation under pathology induced by amyloid-β (Aβ), a primary neurotoxic molecule implicated in AD. We observed that SUMOylation is dysregulated in both human AD brain tissue and the Tg2576 transgenic AD mouse model. While neuronal activation normally induced upregulation of SUMOylation, this effect was impaired by Aβ(42) oligomers. However, supplementing SUMOylation via transduction of its conjugating enzyme, Ubc9, rescued Aβ-induced deficits in LTP and hippocampal-dependent learning and memory. Our data establish SUMO as a novel regulator of LTP and hippocampal-dependent cognition and additionally implicate SUMOylation impairments in AD pathogenesis. Nature Publishing Group 2014-12-02 /pmc/articles/PMC4250909/ /pubmed/25448527 http://dx.doi.org/10.1038/srep07190 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Article
Lee, Linda
Dale, Elena
Staniszewski, Agnes
Zhang, Hong
Saeed, Faisal
Sakurai, Mikako
Fa', Mauro
Orozco, Ian
Michelassi, Francesco
Akpan, Nsikan
Lehrer, Helena
Arancio, Ottavio
Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease
title Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease
title_full Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease
title_fullStr Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease
title_full_unstemmed Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease
title_short Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease
title_sort regulation of synaptic plasticity and cognition by sumo in normal physiology and alzheimer's disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250909/
https://www.ncbi.nlm.nih.gov/pubmed/25448527
http://dx.doi.org/10.1038/srep07190
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