دورية أكاديمية
S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5.
العنوان: | S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5. |
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المؤلفون: | Ferreira CB; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Marttinen M; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany., Coelho JE; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Paldanius KMA; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Takalo M; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Mäkinen P; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Leppänen L; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Miranda-Lourenço C; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Fonseca-Gomes J; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Tanqueiro SR; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Vaz SH; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Belo RF; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Sebastião AM; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Leinonen V; Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland; Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland., Soininen H; Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland., Pike I; Proteome Sciences plc, London, United Kingdom., Haapasalo A; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Lopes LV; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., de Mendonça A; Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Diógenes MJ; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. Electronic address: diogenes@medicina.ulisboa.pt., Hiltunen M; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: mikko.hiltunen@uef.fi. |
المصدر: | Neurobiology of disease [Neurobiol Dis] 2022 Feb; Vol. 163, pp. 105603. Date of Electronic Publication: 2021 Dec 24. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 9500169 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-953X (Electronic) Linking ISSN: 09699961 NLM ISO Abbreviation: Neurobiol Dis Subsets: MEDLINE |
أسماء مطبوعة: | Publication: San Diego, CA : Academic Press Original Publication: Oxford : Blackwell Science, c1994- |
مواضيع طبية MeSH: | Hippocampus/*metabolism , Neurofibrillary Tangles/*metabolism , Septins/*metabolism , Synapses/*metabolism, Animals ; Autophagy/physiology ; Disease Models, Animal ; Hippocampus/pathology ; Humans ; Mice ; Neurofibrillary Tangles/pathology ; Neurons/metabolism ; Neurons/pathology ; Phosphorylation ; Synapses/pathology |
مستخلص: | Alzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynaptic SEPTIN5 protein and its post-translational modifications in the molecular pathogenesis of AD. RNA and protein levels of SEPTIN5 showed a significant decrease in human temporal cortex in relation to the increasing degree of AD-related neurofibrillary pathology. Conversely, an increase in the phosphorylation of the functionally relevant SEPTIN5 phosphorylation site S327 was observed already in the early phases of AD-related neurofibrillary pathology, but not in the cerebrospinal fluid of individuals fulfilling the criteria for mild cognitive impairment due to AD. According to the mechanistic assessments, a link between SEPTIN5 S327 phosphorylation status and the effects of SEPTIN5 on amyloid precursor protein processing and markers of autophagy was discovered in mouse primary cortical neurons transduced with lentiviral constructs encoding wild type SEPTIN5 or SEPTIN5 phosphomutants (S327A and S327D). C57BL/6 J mice intrahippocampally injected with lentiviral wild type SEPTIN5 or phosphomutant constructs did not show changes in cognitive performance after five to six weeks from the start of injections. However, SEPTIN5 S327 phosphorylation status was linked to changes in short-term synaptic plasticity ex vivo at the CA3-CA1 synapse. Collectively, these data suggest that SEPTIN5 and its S327 phosphorylation status play a pivotal role in several cellular processes relevant for AD. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
فهرسة مساهمة: | Keywords: APP processing; Alzheimer's disease; Autophagy; Aβ; Post-translational modifications; SEPTIN5; Synaptic plasticity |
المشرفين على المادة: | EC 3.6.1.- (Sept5 protein, mouse) EC 3.6.1.- (Septins) |
تواريخ الأحداث: | Date Created: 20211226 Date Completed: 20220323 Latest Revision: 20220323 |
رمز التحديث: | 20240628 |
DOI: | 10.1016/j.nbd.2021.105603 |
PMID: | 34954322 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1095-953X |
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DOI: | 10.1016/j.nbd.2021.105603 |