An iPSC-based neural model of sialidosis uncovers glycolytic impairment-causing presynaptic dysfunction and deregulation of Ca

Calcium Signaling / physiology Exocytosis / physiology Glycolysis / physiology Humans Induced Pluripotent Stem Cells Mucolipidoses / physiopathology Neurons / pathology Synapses / pathology
AMPA receptor Exocytosis Glycolysis Lysosomal storage disease Neuraminidase Neurotransmission SNARE protein Sialidosis Voltage dependent Ca(2+) channel iPSC

Journal

Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169

Informations de publication

Date de publication:
05 2021
Historique:
received: 12 02 2020
revised: 22 01 2021
accepted: 25 01 2021
pubmed: 1 2 2021
medline: 4 1 2022
entrez: 31 1 2021
Statut: ppublish

Résumé

Sialidosis is a neuropathic lysosomal storage disease caused by a deficiency in the NEU1 gene-encoding lysosomal neuraminidase and characterized by abnormal accumulation of undigested sialyl-oligoconjugates in systemic organs including brain. Although patients exhibit neurological symptoms, the underlying neuropathological mechanism remains unclear. Here, we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts with sialidosis and induced the differentiation into neural progenitor cells (NPCs) and neurons. Sialidosis NPCs and neurons mimicked the disease-like phenotypes including reduced neuraminidase activity, accumulation of sialyl-oligoconjugates and lysosomal expansions. Functional analysis also revealed that sialidosis neurons displayed two distinct abnormalities, defective exocytotic glutamate release and augmented α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)-mediated Ca

Identifiants

DOI: 10.1016/j.nbd.2021.105279 PMID: 33516873
pubmed: 33516873
pii: S0969-9961(21)00028-0
doi: 10.1016/j.nbd.2021.105279
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

105279

Informations de copyright

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

Auteurs

Haruki Odaka (H)

Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, Ibaraki, Japan.

Tadahiro Numakawa (T)

Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

Minami Soga (M)

Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

Jun Kido (J)

Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Shiro Matsumoto (S)

Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Ryutaro Kajihara (R)

Department of Biomedical Laboratory Sciences, Faculty of Life Science, Kumamoto University, Kumamoto, Japan.

Toshika Okumiya (T)

Department of Biomedical Laboratory Sciences, Faculty of Life Science, Kumamoto University, Kumamoto, Japan.

Naoki Tani (N)

Liaison Laboratory Research Promotion Center, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

Yuki Tanoue (Y)

International Research Center for Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Takaichi Fukuda (T)

Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Hirokazu Furuya (H)

Department of Neurology, Kochi Medical School, Kochi University, Kochi 783-8505, Japan.

Takafumi Inoue (T)

Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.

Takumi Era (T)

Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. Electronic address: tera@kumamoto-u.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Systèmes de seconds messagers › Signalisation calcique › An iPSC-based neural model of sialidosis...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Exocytose › An iPSC-based neural model of sialidosis...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Glycolyse › An iPSC-based neural model of sialidosis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › An iPSC-based neural model of sialidosis...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches pluripotentes induites › An iPSC-based neural model of sialidosis...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Erreurs innées du métabolisme › Maladies lysosomiales › Maladies neurologiques de surcharge lysosomiale › Mucolipidoses › An iPSC-based neural model of sialidosis...
questionsmedicales.fr › Cellules › Neurones › An iPSC-based neural model of sialidosis...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Jonctions intercellulaires › Synapses › An iPSC-based neural model of sialidosis...