{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:31:49Z","timestamp":1789453909075,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IFN-\u03b1 is widely used for the treatment of chronic viral hepatitis and malignancies. However, systemic IFN-\u03b1 treatment causes severe neuropsychiatric complications in humans, including depression, anxiety, and cognitive impairments. We have previously reported that the fusion protein formed by IFN-\u03b1 and apolipoprotein A-I (IA) circulates bound to high-density lipoproteins (HDLs) and exhibits liver targeting, increased half-life, enhanced immunostimulatory activity, and reduced cytotoxicity. As the transport of HDLs across the blood\u2013brain barrier is a highly complex and regulated process, in this study, we examine the effects of IA on the brain. Determination of IFN-\u03b1 in brain and serum after hydrodynamic administration of different doses of a plasmid encoding IFN-\u03b1 or IA showed that IA penetrated into the brain by a saturable transport mechanism. Thus, at high serum levels of the transgenes, the induction of IFN-sensitive genes and the number of phospho-STAT1+ cell nuclei in the brain were substantially higher with IFN-\u03b1 than with IA. This was associated with attenuation of neurodepression in mice given IA, as manifested by shorter immobility time in the tail suspension test. However, when given low doses of rIFN-\u03b1 or the same antiviral units of HDLs containing IA, the induction of IFN-stimulated genes in the brain was significantly greater with the latter. In conclusion, IA crosses the blood\u2013brain barrier not by diffusion, as is the case of IFN-\u03b1, but by a facilitated saturable transport mechanism. Thus, linkage to apolipoprotein A-I may serve to modulate the effects of IFN-\u03b1 on the CNS.<\/jats:p>","DOI":"10.4049\/jimmunol.1101598","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T07:33:41Z","timestamp":1331796821000},"page":"3988-3992","source":"Crossref","is-referenced-by-count":18,"title":["The Fusion Protein of IFN-\u03b1 and Apolipoprotein A-I Crosses the Blood\u2013Brain Barrier by a Saturable Transport Mechanism"],"prefix":"10.1093","volume":"188","author":[{"given":"Jessica","family":"Fioravanti","sequence":"first","affiliation":[{"name":"Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra , Pamplona, Navarra 31008 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Medina-Echeverz","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra , Pamplona, Navarra 31008 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Ardaiz","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra , Pamplona, Navarra 31008 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Gomar","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra , Pamplona, Navarra 31008 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinnia P","family":"Parra-Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra , Pamplona, Navarra 31008 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Prieto","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra , Pamplona, Navarra 31008 ,","place":["Spain"]},{"name":"Networked Biomedical Research Center of Hepatic and Digestive Diseases, Clinic of the University of Navarra , Pamplona, Navarra 31008 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Berraondo","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra , Pamplona, Navarra 31008 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,4,15]]},"reference":[{"key":"2025032410021694400_r1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1098\/rspb.1957.0048","article-title":"Virus interference. 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