{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:35:18Z","timestamp":1791308118807,"version":"4.3.1"},"reference-count":253,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,8]],"date-time":"2018-12-08T00:00:00Z","timestamp":1544227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014-23211-0"],"award-info":[{"award-number":["2014-23211-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["32355-2017-0"],"award-info":[{"award-number":["32355-2017-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Coordena\u00e7\u00e3o de Pessoal de N\u00edvel Superior","award":["Financial code 001"],"award-info":[{"award-number":["Financial code 001"]}]},{"name":"Funda\u00e7\u00e3o de Apoio ao Ensino, Pesquisa e Assist\u00eancia do Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo","award":["2017"],"award-info":[{"award-number":["2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>For decades, neurological, psychological, and cognitive alterations, as well as other glandular manifestations (EGM), have been described and are being considered to be part of Sj\u00f6gren\u2019s syndrome (SS). Dry eye and dry mouth are major findings in SS. The lacrimal glands (LG), ocular surface (OS), and salivary glands (SG) are linked to the central nervous system (CNS) at the brainstem and hippocampus. Once compromised, these CNS sites may be responsible for autonomic and functional disturbances that are related to major and EGM in SS. Recent studies have confirmed that the kynurenine metabolic pathway (KP) can be stimulated by interferon-\u03b3 (IFN-\u03b3) and other cytokines, activating indoleamine 2,3-dioxygenase (IDO) in SS. This pathway interferes with serotonergic and glutamatergic neurotransmission, mostly in the hippocampus and other structures of the CNS. Therefore, it is plausible that KP induces neurological manifestations and contributes to the discrepancy between symptoms and signs, including manifestations of hyperalgesia and depression in SS patients with weaker signs of sicca, for example. Observations from clinical studies in acquired immune deficiency syndrome (AIDS), graft-versus-host disease, and lupus, as well as from experimental studies, support this hypothesis. However, the obtained results for SS are controversial, as discussed in this study. Therapeutic strategies have been reexamined and new options designed and tested to regulate the KP. In the future, the confirmation and application of this concept may help to elucidate the mosaic of SS manifestations.<\/jats:p>","DOI":"10.3390\/ijms19123953","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T03:36:41Z","timestamp":1544413001000},"page":"3953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Neurological and Inflammatory Manifestations in Sj\u00f6gren\u2019s Syndrome: The Role of the Kynurenine Metabolic Pathway"],"prefix":"10.3390","volume":"19","author":[{"given":"Fab\u00edola Reis","family":"De Oliveira","sequence":"first","affiliation":[{"name":"Ribeirao Preto Medical School, Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP 14049-900 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5259-7513","authenticated-orcid":false,"given":"Marina Zilio","family":"Fantucci","sequence":"additional","affiliation":[{"name":"Ribeirao Preto Medical School, Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP 14049-900 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leidiane","family":"Adriano","sequence":"additional","affiliation":[{"name":"Ribeirao Preto Medical School, Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP 14049-900 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ria","family":"Valim","sequence":"additional","affiliation":[{"name":"Esp\u00edrito Santo Federal University, Vitoria, ES 29075-910, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Mattar","family":"Cunha","sequence":"additional","affiliation":[{"name":"Ribeirao Preto Medical School, Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP 14049-900 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Louzada-Junior","sequence":"additional","affiliation":[{"name":"Ribeirao Preto Medical School, Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP 14049-900 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-7313","authenticated-orcid":false,"given":"Eduardo Melani","family":"Rocha","sequence":"additional","affiliation":[{"name":"Ribeirao Preto Medical School, Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP 14049-900 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/ard.61.6.554","article-title":"Classification criteria for Sj\u00f6gren\u2019s syndrome: A revised version of the European criteria proposed by the American-European Consensus Group","volume":"61","author":"Vitali","year":"2002","journal-title":"Ann. 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