Amyloid precursor protein induces reactive astrogliosis

We present and evidence demonstrating that Amyloid Precursor Protein (APP) acts as an essential instigator of reactive astrogliosis. Cell-specific overexpression of APP in cultured astrocytes led to remodelling of the intermediate filament network, enhancement of cytokine production and activation o...

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Published inbioRxiv : the preprint server for biology
Main Authors Jauregui, Gretsen Velezmoro, Vukić, Dragana, Onyango, Isaac G, Arias, Carlos, Novotný, Jan S, Texlová, Kateřina, Wang, Shanshan, Kovačovicova, Kristina Locker, Polakova, Natalie, Zelinkova, Jana, Čarna, Maria, Strašil, Valentina Lacovich, Head, Brian P, Havas, Daniel, Mistrik, Martin, Zorec, Robert, Verkhratsky, Alexei, Keegan, Liam, O'Connel, Mary, Rissman, Robert, Stokin, Gorazd B
Format Journal Article
LanguageEnglish
Published United States 18.12.2023
Subjects
reactive astrogliosis
amyloid precursor protein
traumatic brain injury
astrocytes
interferon pathway
lipopolysaccharide
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Summary:We present and evidence demonstrating that Amyloid Precursor Protein (APP) acts as an essential instigator of reactive astrogliosis. Cell-specific overexpression of APP in cultured astrocytes led to remodelling of the intermediate filament network, enhancement of cytokine production and activation of cellular programs centred around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion in cultured astrocytes abrogated remodelling of the intermediate filament network and blunted expression of IFN stimulated gene (ISG) products in response to lipopolysaccharide (LPS). 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 (GFAP) observed canonically in astrocytes in response to TBI. Thus, APP represents a molecular inducer and regulator of reactive astrogliosis.