Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients.

Autosomal-recessive hereditary spastic paraplegia Disease-associated microglia IFNγ/ STAT1 signaling Induced microglia-like cells Inflammation Multisystem neurodegeneration

Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
02 Feb 2024
Historique:
received: 25 10 2023
accepted: 22 12 2023
revised: 15 12 2023
medline: 2 2 2024
pubmed: 2 2 2024
entrez: 2 2 2024
Statut: epublish

Résumé

Biallelic loss of SPG11 function constitutes the most frequent cause of complicated autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum, resulting in progressive multisystem neurodegeneration. While the impact of neuroinflammation is an emerging and potentially treatable aspect in neurodegenerative diseases and leukodystrophies, the role of immune cells in SPG11-HSP patients is unknown. Here, we performed a comprehensive immunological characterization of SPG11-HSP, including examination of three human postmortem brain donations, immunophenotyping of patients' peripheral blood cells and patient-specific induced pluripotent stem cell-derived microglia-like cells (iMGL). We delineate a previously unknown role of innate immunity in SPG11-HSP. Neuropathological analysis of SPG11-HSP patient brain tissue revealed profound microgliosis in areas of neurodegeneration, downregulation of homeostatic microglial markers and cell-intrinsic accumulation of lipids and lipofuscin in IBA1

Identifiants

pubmed: 38305941
doi: 10.1007/s00401-023-02675-w
pii: 10.1007/s00401-023-02675-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

28

Subventions

Organisme : Bundesministerium für Bildung und Forschung
ID : 01GM1905B
Organisme : Bundesministerium für Bildung und Forschung
ID : 01GM2209B
Organisme : Bundesministerium für Bildung und Forschung
ID : 01EO2105
Organisme : Bundesministerium für Bildung und Forschung
ID : 01GM2209C
Organisme : Deutsche Forschungsgemeinschaft
ID : 270949263
Organisme : Deutsche Forschungsgemeinschaft
ID : 505539112
Organisme : Deutsche Forschungsgemeinschaft
ID : FOG2625 HU 800/13-2
Organisme : EU Horizon 2020 program
ID : 779257
Organisme : Senior Clinical Researcher mandate of the Research Fund - Flanders (FWO)
ID : 1805021N

Informations de copyright

© 2024. The Author(s).

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Auteurs

Laura Krumm (L)

Department of Stem Cell Biology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.

Tatyana Pozner (T)

Department of Stem Cell Biology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.

Naime Zagha (N)

Department of Stem Cell Biology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.

Roland Coras (R)

Department of Neuropathology, FAU Erlangen-Nürnberg, Erlangen, Germany.

Philipp Arnold (P)

Institute of Functional and Clinical Anatomy, FAU Erlangen-Nürnberg, Erlangen, Germany.

Thanos Tsaktanis (T)

Department of Neurology, University Hospital Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Kathryn Scherpelz (K)

Division of Neuropathology, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.

Marie Y Davis (MY)

Department of Neurology, University of Washington Medical Center, Seattle, WA, USA.
VA Puget Sound Healthcare System, Seattle, WA, USA.

Johanna Kaindl (J)

Department of Stem Cell Biology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.

Iris Stolzer (I)

Department of Medicine 1, University Hospital Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Patrick Süß (P)

Department of Neurology, University Hospital Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Mukhran Khundadze (M)

Institute of Human Genetics, Jena University Hospital Friedrich-Schiller-University Jena, Jena, Germany.

Christian A Hübner (CA)

Institute of Human Genetics, Jena University Hospital Friedrich-Schiller-University Jena, Jena, Germany.
Center for Rare Diseases, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.

Markus J Riemenschneider (MJ)

Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.

Jonathan Baets (J)

Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Neuromuscular Reference Centre, Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.

Claudia Günther (C)

Department of Medicine 1, University Hospital Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Kussmaulallee 4, 91054, Erlangen, Germany.

Suman Jayadev (S)

Department of Neurology, University of Washington Medical Center, Seattle, WA, USA.
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Division of Medical Genetics, University of Washington, Seattle, WA, USA.

Veit Rothhammer (V)

Department of Neurology, University Hospital Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Florian Krach (F)

Department of Stem Cell Biology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.

Jürgen Winkler (J)

Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.
Department of Molecular Neurology, FAU Erlangen-Nürnberg, Erlangen, Germany.

Beate Winner (B)

Department of Stem Cell Biology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Martin Regensburger (M)

Department of Stem Cell Biology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany. martin.regensburger@uk-erlangen.de.
Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Kussmaulallee 4, 91054, Erlangen, Germany. martin.regensburger@uk-erlangen.de.
Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany. martin.regensburger@uk-erlangen.de.
Department of Molecular Neurology, FAU Erlangen-Nürnberg, Erlangen, Germany. martin.regensburger@uk-erlangen.de.

Classifications MeSH