期刊论文详细信息
Neurobiology of Disease
Cyclophillin A deficiency accelerates RML-induced prion disease
Valentina Bonetto1  Laura Pasetto1  Ihssane Bouybayoune2  Ilaria Bertani2  Roberto Chiesa2  Liliana Comerio2 
[1] Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy;Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy;
关键词: Protein misfolding;    Prion protein;    PrP;    Scrapie;    PPIA;    Microglia;   
DOI  :  
来源: DOAJ
【 摘 要 】

Prion diseases typically involve brain deposition of abnormally folded prion protein, which is associated with activated glia and increased cytokine production. Cyclophilin A (CypA) is a ubiquitous protein with peptidyl prolyl cis-trans isomerase activity, which regulates protein folding, and can be secreted by cells in response to inflammatory stimuli. On the basis of in vitro studies, CypA was proposed to mediate glial activation during prion infection. To investigate the role of CypA in vivo, we inoculated CypA+/+, CypA+/− and CypA−/− mice with the RML prion strain, and recorded the time to onset of neurological signs and to terminal disease, and the astrocyte and microglia response at presymptomatic and symptomatic stages. Time to onset of disease and survival were significantly shorter in CypA-deficient mice than CypA-expressing controls. CypA-deficient mice had significantly greater microglial activation in the presymptomatic stage, and analysis of anti- and pro-inflammatory microglial markers indicated a shift towards a pro-inflammatory phenotype. There was no difference in astrocyte activation. This suggests that CypA contributes to dampening the pro-inflammatory microglial response during the early stage of RML-induced prion disease.

【 授权许可】

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