{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T04:46:39Z","timestamp":1787460399842,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Roche SpA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for both Relapsing and Primary Progressive forms of Multiple Sclerosis (MS) treatment. OCR is postulated to act via rapid B cell depletion; however, by analogy with other anti-CD20 agents, additional effects can be envisaged, such as on Protein Kinase C (PKC). Hence, this work aims to explore novel potential mechanisms of action of OCR in peripheral blood mononuclear cells from MS patients before and after 12 months of OCR treatment. We first assessed, up-stream, PKC\u03b2II and subsequently explored two down-stream pathways: hypoxia-inducible factor 1 alpha (HIF-1\u03b1)\/vascular endothelial growth factor (VEGF), and human antigen R (HuR)\/manganese-dependent superoxide dismutase (MnSOD) and heat shock proteins 70 (HSP70). At baseline, higher levels of PKC\u03b2II, HIF-1\u03b1, and VEGF were found in MS patients compared to healthy controls (HC); interestingly, the overexpression of this inflammatory cascade was counteracted by OCR treatment. Conversely, at baseline, the content of HuR, MnSOD, and HSP70 was significantly lower in MS patients compared to HC, while OCR administration induced the up-regulation of these neuroprotective pathways. These results enable us to disclose the dual positive action of OCR: anti-inflammatory and neuroprotective. Therefore, in addition to B cell depletion, the effect of OCR on these molecular cascades can contribute to counteracting disease progression.<\/jats:p>","DOI":"10.3390\/ijms25168923","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T06:23:20Z","timestamp":1723789400000},"page":"8923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Disclosing the Novel Protective Mechanisms of Ocrelizumab in Multiple Sclerosis: The Role of PKC Beta and Its Down-Stream Targets"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6680-216X","authenticated-orcid":false,"given":"Lucrezia Irene Maria","family":"Campagnoli","sequence":"first","affiliation":[{"name":"Department of Drug Sciences, Section of Pharmacology, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2463-6815","authenticated-orcid":false,"given":"Lara","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6271-1420","authenticated-orcid":false,"given":"Nicoletta","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, Section of Pharmacology, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8097-0565","authenticated-orcid":false,"given":"Giacomo","family":"Greco","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3192-6397","authenticated-orcid":false,"given":"Federica","family":"Boschi","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, Section of Pharmacology, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7048-6307","authenticated-orcid":false,"given":"Francesco","family":"Masi","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0031-9594","authenticated-orcid":false,"given":"Giulia","family":"Mallucci","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1397-511X","authenticated-orcid":false,"given":"Roberto","family":"Bergamaschi","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Colombo","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-4272","authenticated-orcid":false,"given":"Alessia","family":"Pascale","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, Section of Pharmacology, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple Sclerosis\u2014A review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur. 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