{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:15:30Z","timestamp":1787652930140,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroinflammation and autoimmune mechanisms have a key part in the pathogenesis of Parkinson\u2019s disease (PD). Therefore, we evaluated the role of Toll-like receptors (TLRs) as a link between inflammation and autoimmunity in PD. An in vivo model of PD was performed by administration of 1-metil 4-fenil 1,2,3,6-tetraidro-piridina (MPTP) at the dose of 20 mg\/kg every 2 h for a total administration of 80\/kg, both in single Knock Out (KO) mice for TLR7, TLR 8, and TLR9 and in double KO mice for TLR 7\/8-\/-. All animals were compared with WT animals used as a control group. All animals were sacrificed after 7 days form the first administration of MPTP. The genetic absence of TLR 7 and 8 modified the PD pathway, increasing the immunoreactivity for TH and DAT compared to PD groups and decreasing microglia and astrocytes activation. Moreover, the deletion of TLR7 and TLR8 significantly reduced T-cell infiltration in the substantia nigra and lymph nodes, suggesting a reduction of T-cell activation. Therefore, our result highlights a possibility that an immunotherapy approach, by using a dual antagonist of TLR 7 and 8, could be considered as a possible target to develop new therapies for Parkinson diseases.<\/jats:p>","DOI":"10.3390\/ijms21249384","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:45:03Z","timestamp":1607561103000},"page":"9384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["TLR7\/8 in the Pathogenesis of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Michela","family":"Campolo","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Filippone","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Biondo","sequence":"additional","affiliation":[{"name":"Metchnikoff Laboratory, Department of Human Pathology and Medicine, University of Messina, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-3228","authenticated-orcid":false,"given":"Giuseppe","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Metchnikoff Laboratory, Department of Human Pathology and Medicine, University of Messina, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Casili","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Lanza","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-3690","authenticated-orcid":false,"given":"Salvatore","family":"Cuzzocrea","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019alcontres, 31-98166 Messina, Italy"},{"name":"Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-6387","authenticated-orcid":false,"given":"Emanuela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Paterniti","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s12035-012-8280-y","article-title":"The Lewy body in Parkinson\u2019s disease and related neurodegenerative disorders","volume":"47","author":"Wakabayashi","year":"2013","journal-title":"Mol. 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