Oxidized/deamidated-ceruloplasmin dysregulates choroid plexus epithelial cells functionality and barrier properties via RGD-recognizing integrin binding

NEUROBIOLOGY OF DISEASE

卷:158

Article

Zanardi, Alan¹  Barbariga, Marco¹  Conti, Antonio¹  Vegliani, Franco¹  Flavio, Curnis²  Alessio, Massimo¹ 

[1] IRCCS Osped San Raffaele, Proteome Biochem, Via Olgettina 58, I-20132 Milan, Italy

[2] IRCCS Osped San Raffaele, Tumor Biol & Vasc Targeting, I-20132 Milan, Italy

关键词: Ceruloplasmin;    Choroid plexus;    Blood-cerebrospinal fluid barrier;    Deamidation;    Oxidation;    Secretome;    Neurodegeneration;    Cerebrospinal fluid;    Parkinson's disease;   

DOI  :  10.1016/j.nbd.2021.105474

来源: Elsevier

【 摘 要 】

Choroid plexus epithelial cells (CPEpiCs) determine the composition of cerebrospinal fluid (CSF) and constitute the blood-CSF barrier (BCSFB), functions that are altered in neurodegenerative diseases. In Parkinson's disease (PD) the pathological environment oxidizes and deamidates the ceruloplasmin, a CSF-resident ferroxidase, which undergoes a gain of RGD-recognizing integrin binding property, that may result in signal transduction. We investigated the effects that oxidized/deamidated ceruloplasmin (Cp-ox/de) may exert on CPEpiCs functions. Through RGD-recognizing integrins binding, Cp-ox/de mediates CPEpiCs adhesion and intracellular signaling, resulting in cell proliferation inhibition and alteration of the secretome profile in terms of proteins related to cellextracellular matrix interaction. Oxidative conditions, comparable to those found in the CSF of PD patients, induced CPEpiCs barrier leakage, allowing Cp-ox/de to cross it, transducing integrins-mediated signal that further worsens BCSFB integrity. This mechanism might contribute to PD pathological processes altering CSF composition and aggravating the already compromised BCSFB function.