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Amyloid precursor protein induces reactive astrogliosis
G. Velezmoro Jauregui, D. Vukić, IG. Onyango, C. Arias, JS. Novotný, K. Texlová, S. Wang, KL. Kovačovicova, N. Polakova, J. Zelinkova, M. Čarna, V. Lacovich, BP. Head, D. Havas, M. Mistrik, R. Zorec, A. Verkhratsky, L. Keegan, MA. O'Connell, R....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
(EXCELES, LX22NPO5107 (MEYS)) (G.B.S.)
The European Union: Next Generation EU - Project National Institute for Neurological Research
J3-50104 (R.Z.)
The Slovenian Research Agency project
21-27329X (M.A.O. and L.K.)
The Czech Science Foundation GAČR
The Slovenian Research Agency Core Research Program P3 310 Cell Physiology (R.Z.)
CZ.02.1.01/0.0./15_003/0000492 (G.B.S.)
The European Regional Development MAGNET
CZ02.1.01/0.0/16_019/0000868 (G.B.S.)
The European Regional Development ENOCH
Interreg ITA-SLO ImmunoCluster-2; CipKeBip (R.Z.)
5I01BX003671 (B.P.H.)
VA Merit Award
1IK6BX006318 (B.P.H.)
VA Research Career Scientist Award
PubMed
38584589
DOI
10.1111/apha.14142
Knihovny.cz E-zdroje
- MeSH
- amyloidový prekurzorový protein beta * metabolismus genetika MeSH
- astrocyty * metabolismus patologie MeSH
- glióza * metabolismus patologie MeSH
- kultivované buňky MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- traumatické poranění mozku metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
AIM: Astrocytes respond to stressors by acquiring a reactive state characterized by changes in their morphology and function. Molecules underlying reactive astrogliosis, however, remain largely unknown. Given that several studies observed increase in the Amyloid Precursor Protein (APP) in reactive astrocytes, we here test whether APP plays a role in reactive astrogliosis. METHODS: We investigated whether APP instigates reactive astroglios by examining in vitro and in vivo the morphology and function of naive and APP-deficient astrocytes in response to APP and well-established stressors. RESULTS: Overexpression of APP in cultured astrocytes led to remodeling of the intermediate filament network, enhancement of cytokine production, and activation of cellular programs centered around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion abrogated remodeling of the intermediate filament network and blunted expression of IFN-stimulated gene products in response to lipopolysaccharide. Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein observed canonically in astrocytes in response to TBI. CONCLUSIONS: The APP thus represents a candidate molecular inducer and regulator of reactive astrogliosis. This finding has implications for understanding pathophysiology of neurodegenerative and other diseases of the nervous system characterized by reactive astrogliosis and opens potential new therapeutic avenues targeting APP and its pathways to modulate reactive astrogliosis.
Achucarro Centre for Neuroscience IIKERBASQUE Basque Foundation for Science Bilbao Spain
Celica Biomedical Technology Park Ljubljana Slovenia
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Anesthesia University of California San Diego La Jolla California USA
Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Neurosciences University of California San Diego La Jolla California USA
Faculty of Biology Medicine and Health University of Manchester Manchester UK
Faculty of Science National Centre for Biomedical Research Masaryk University Brno Czech Republic
Citace poskytuje Crossref.org
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