Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain.
Nat. Med. 29, 3149–3161 (2023)
The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood-brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
3 Binding-protein; Reactive Astrocytes; Progenitor Cells; Neural Stem; Biomarkers; Lgals3bp; Lectin; Growth; Cancer; Tissue
ISSN (print) / ISBN
1078-8956
e-ISSN
1546-170X
Zeitschrift
Nature medicine
Quellenangaben
Band: 29,
Seiten: 3149–3161
Verlag
Nature Publishing Group
Verlagsort
New York, NY
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Förderungen
SyNergy (EXC2145)
SPP 2306 Ferroptosis
German Research Foundation
Advanced ERC grant
European Union's Horizon 2020 research and innovation program
SPP 2306 Ferroptosis
German Research Foundation
Advanced ERC grant
European Union's Horizon 2020 research and innovation program