Altered conformation of α-synuclein drives dysfunction of synaptic vesicles in a synaptosomal model of Parkinson's disease.

Animals Brain / pathology Calcium / metabolism Disease Models, Animal Exocytosis Humans Hydrogen-Ion Concentration Magnetic Resonance Spectroscopy Models, Biological Parkinson Disease / metabolism Protein Conformation Protein Folding Protein Multimerization Recombinant Proteins / metabolism SNARE Proteins / metabolism Solubility Synaptic Vesicles / metabolism Synaptosomes / metabolism alpha-Synuclein / chemistry
Parkinson’s disease alpha-synuclein in-cell NMR neurodegeneration post-translational modifications protein folding synapse

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
06 07 2021
Historique:
received: 21 08 2020
revised: 30 12 2020
accepted: 10 06 2021
entrez: 7 7 2021
pubmed: 8 7 2021
medline: 11 2 2022
Statut: ppublish

Résumé

While misfolding of alpha-synuclein (αSyn) is central to the pathogenesis of Parkinson's disease (PD), fundamental questions about its structure and function at the synapse remain unanswered. We examine synaptosomes from non-transgenic and transgenic mice expressing wild-type human αSyn, the E46K fPD-causing mutation, or an amplified form of E46K ("3K"). Synaptosomes from mice expressing the 3K mutant show reduced Ca

Identifiants

DOI: 10.1016/j.celrep.2021.109333 PMID: 34233191 PMC: PMC8552450
pubmed: 34233191
pii: S2211-1247(21)00709-9
doi: 10.1016/j.celrep.2021.109333
pmc: PMC8552450
mid: NIHMS1747464
pii:
doi:

Substances chimiques

Recombinant Proteins 0
SNARE Proteins 0
alpha-Synuclein 0
Calcium SY7Q814VUP

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

109333

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS083845
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS109510
Pays : United States
Organisme : NINDS NIH HHS
ID : RF1 NS083845
Pays : United States

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests D.J.S. is a director of and consultant to Prothena Biosciences. All other authors declare no competing interests.

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Auteurs

Luis Fonseca-Ornelas (L)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Thibault Viennet (T)

Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Matteo Rovere (M)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Haiyang Jiang (H)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Lei Liu (L)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Silke Nuber (S)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Maria Ericsson (M)

Electron Microscopy Laboratory, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Haribabu Arthanari (H)

Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Dennis J Selkoe (DJ)

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: dselkoe@bwh.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Calcium › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Exocytose › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Phénomènes chimiques › Concentration en ions d'hydrogène › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Analyse spectrale › Spectroscopie par résonance magnétique › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladie de Parkinson › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Pliage des protéines › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Multimérisation de protéines › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines recombinantes › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines du transport vésiculaire › Protéines SNARE › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Phénomènes chimiques › Solubilité › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Vésicules cytoplasmiques › Vésicules de transport › Vésicules de sécrétion › Vésicules synaptiques › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Synaptosomes › Altered conformation of α-synuclein drives...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › alpha-Synucléine › Altered conformation of α-synuclein drives...