Amyloid precursor protein induces reactive astrogliosis

• DOI: 10.1111/apha.14142
• Publication Date: 2024-04-08T08:05:43Z
• Authors: Gretsen Velezmoro...; Dragana Vukić; Isaac G. Onyango; Carlos Arias; Jan S. Novotný; Kateřina Texlová; Shanshan Wang; Kristina Locker K...; Natalie Polakova; Jana Zelinkova; Maria Čarna; Valentina Lacovich; Brian P. Head; Daniel Havas; Martin Mistrik; Robert Zorec; Alexei Verkhratsky; Liam Keegan; Mary A. O'Connell; Robert Rissman; Gorazd B. Stokin
• Keywords: Astrogliosis

Abstract Aim Astrocytes respond to stressors by acquiring a reactive state characterized changes in their morphology and function. Molecules underlying astrogliosis, however, remain largely unknown. Given that several studies observed increase the Amyloid Precursor Protein (APP) astrocytes, we here test whether APP plays role astrogliosis. Methods We investigated instigates astroglios examining vitro vivo function of naive APP‐deficient astrocytes response well‐established stressors. Results Overexpression cultured led remodeling intermediate filament network, enhancement cytokine production, activation cellular programs centered around interferon (IFN) pathway, all signs Conversely, deletion abrogated network blunted expression IFN‐stimulated gene products lipopolysaccharide. Following traumatic brain injury (TBI), mouse also exhibited an association between IFN, while curbed glial fibrillary acidic protein canonically TBI. Conclusions The thus represents candidate molecular inducer regulator This finding has implications for understanding pathophysiology neurodegenerative other diseases nervous system astrogliosis opens potential new therapeutic avenues targeting its pathways modulate