{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:11:08Z","timestamp":1760145068308,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Egas Moniz School of Health and Science"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Microbial dysbiosis may contribute to alpha-synuclein (\u03b1-Syn) homeostasis disruption, yet the burden of inflammatory periodontal infection and its treatment have never been studied in this regard. We aimed to compare the cytokine and \u03b1-Syn levels in the saliva and blood of patients with periodontitis who underwent non-surgical periodontal therapy (NSPT) and those of their healthy counterparts. Methods: Periodontal examination and saliva and blood sample collection were carried out in incoming patients at a university clinic. The periodontitis group (PG) received NSPT. The sample collection and periodontal observation were repeated 30 days after. IL-6, IL1-\u03b2 and total \u03b1-Syn were quantified using immunoassay methods. The periodontal inflamed surface area (PISA) was calculated as a proxy for periodontal inflammation. Results: Eleven participants formed the PG, and there were fifteen healthy controls (HC). At baseline, no correlation between salivary and plasma \u03b1-Syn was found. The salivary \u03b1-Syn levels revealed a tendency to decrease 30 days after, particularly in the PD cases. The variation in PISA and \u03b1-Syn showed significant correlation. Salivary \u03b1-Syn correlated negatively with salivary IL-6 levels at both timepoints in the total sample (rho = \u22120.394 and rho = \u22120.451) and in the HC (rho = \u22120.632 and rho = \u22120.561). Variations in plasma IL-6 and \u03b1-Syn were negatively correlated (rho = \u22120.518) in the healthy participants. Baseline plasma IL1-\u03b2 negatively correlated with plasmatic \u03b1-Syn at 30 days in the HC (rho = \u22120.581). Conclusions: Salivary and plasma \u03b1-Syn bioavailability operate independently, and periodontal diagnosis was not a confounding factor. Salivary \u03b1-Syn levels were significantly affected by NSPT, contrary to plasma levels. These results should be confirmed in future larger and prospective studies.<\/jats:p>","DOI":"10.3390\/jcm13123586","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T08:06:06Z","timestamp":1718784366000},"page":"3586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non-Surgical Periodontal Therapy\u2019s Influence on Alpha-Synuclein and Inflammatory Marker Levels: A Pilot Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6804-9124","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Lyra","sequence":"first","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1019-8263","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Botelho","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-9797","authenticated-orcid":false,"given":"Silvia","family":"Rota","sequence":"additional","affiliation":[{"name":"Department of Basic & Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London, London WC2R 2LS, UK"},{"name":"Parkinson\u2019s Foundation Center of Excellence, King\u2019s College Hospital, London SE5 9RS, UK"}]},{"given":"Karolina","family":"Poplawska-Domaszewicz","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Foundation Center of Excellence, King\u2019s College Hospital, London SE5 9RS, UK"},{"name":"Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2503-260X","authenticated-orcid":false,"given":"Vanessa","family":"Machado","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7181-4028","authenticated-orcid":false,"given":"Daniela","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-5936","authenticated-orcid":false,"given":"Lu\u00eds","family":"Proen\u00e7a","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4098-5433","authenticated-orcid":false,"given":"Helena","family":"Barroso","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0167-4077","authenticated-orcid":false,"given":"Jos\u00e9 Jo\u00e3o","family":"Mendes","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-0505","authenticated-orcid":false,"given":"Kallol Ray","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Department of Basic & Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London, London WC2R 2LS, UK"},{"name":"Parkinson\u2019s Foundation Center of Excellence, King\u2019s College Hospital, London SE5 9RS, UK"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1523\/JNEUROSCI.4564-06.2007","article-title":"Presynaptic \u03b1-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with lewy bodies","volume":"27","author":"Kramer","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ane.12247","article-title":"Alpha-synuclein in peripheral tissues and body fluids as a biomarker for Parkinson\u2019s disease\u2014A systematic review","volume":"130","author":"Malek","year":"2014","journal-title":"Acta Neurol. Scand."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lyra, P., Machado, V., Rota, S., Chaudhuri, K.R., Botelho, J., and Mendes, J.J. (2023). Revisiting Alpha-Synuclein Pathways to Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087137"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fnins.2016.00408","article-title":"Alpha-Synuclein Oligomers\u2014Neurotoxic Molecules in Parkinson\u2019s Disease and Other Lewy Body Disorders","volume":"10","author":"Ingelsson","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13024-020-00368-6","article-title":"Initiation and propagation of \u03b1-synuclein aggregation in the nervous system","volume":"15","author":"Hijaz","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nature14547","article-title":"\u03b1-Synuclein strains cause distinct synucleinopathies after local and systemic administration","volume":"522","author":"Peelaerts","year":"2015","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.3389\/fneur.2019.01388","article-title":"Plasma and Serum Alpha-Synuclein as a Biomarker of Diagnosis in Patients With Parkinson\u2019s Disease","volume":"10","author":"Chang","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s00702-019-02062-4","article-title":"Salivary alpha-synuclein as a biomarker for Parkinson\u2019s disease: A systematic review","volume":"126","author":"Bougea","year":"2019","journal-title":"J. Neural Transm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"28143","DOI":"10.1038\/srep28143","article-title":"Salivary total \u03b1-synuclein, oligomeric \u03b1-synuclein and SNCA variants in Parkinson\u2019s disease patients","volume":"6","author":"Kang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vivacqua, G., Latorre, A., Suppa, A., Nardi, M., Pietracupa, S., Mancinelli, R., Fabbrini, G., Colosimo, C., Gaudio, E., and Berardelli, A. (2016). Abnormal salivary total and oligomeric alpha-synuclein in Parkinson\u2019s disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151156"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41531-022-00357-0","article-title":"Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson\u2019s disease and other synucleinopathies","volume":"8","author":"Lashuel","year":"2022","journal-title":"NPJ Park. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The Parkinson pandemic\u2014A call to action","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"L\u00e1zaro, D.F., Rodrigues, E.F., Langohr, R., Shahpasandzadeh, H., Ribeiro, T., Guerreiro, P., Gerhardt, E., Kr\u00f6hnert, K., Klucken, J., and Pereira, M.D. (2014). Systematic Comparison of the Effects of Alpha-synuclein Mutations on Its Oligomerization and Aggregation. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004741"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/jnen\/62.6.644","article-title":"Accumulation of phosphorylated \u03b1-synuclein in aging human brain","volume":"62","author":"Yuko","year":"2003","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"446582","DOI":"10.3389\/fnins.2019.00369","article-title":"Alpha-synuclein pathology and the role of the microbiota in Parkinson\u2019s disease","volume":"13","author":"Fitzgerald","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/jcpe.12732","article-title":"Impact of the global burden of periodontal diseases on health, nutrition and wellbeing of mankind: A call for global action","volume":"44","author":"Tonetti","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/JPER.21-0111","article-title":"Economic burden of periodontitis in the United States and Europe\u2014An updated estimation","volume":"93","author":"Botelho","year":"2021","journal-title":"J. Periodontol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"K\u00f6n\u00f6nen, E., Gursoy, M., and Gursoy, U. (2019). Periodontitis: A Multifaceted Disease of Tooth-Supporting Tissues. J. Clin. Med., 8.","DOI":"10.3390\/jcm8081135"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41577-020-00488-6","article-title":"Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities","volume":"21","author":"Hajishengallis","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/jcpe.12881","article-title":"Ageing effects on humoral immune responses in chronic periodontitis","volume":"45","author":"Ebersole","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Botelho, J., Leira, Y., Viana, J., Machado, V., Lyra, P., Aldrey, J.M., P\u00edas-Peleteiro, J.M., Blanco, J., Sobrino, T., and Mendes, J.J. (2021). The Role of Inflammatory Diet and Vitamin D on the Link between Periodontitis and Cognitive Function: A Mediation Analysis in Older Adults. Nutrients, 13.","DOI":"10.3390\/nu13030924"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lyra, P., Machado, V., Proen\u00e7a, L., Domingos, J., Godinho, C., Mendes, J.J., and Botelho, J. (2020). Parkinson\u2019s disease, periodontitis and patient-related outcomes: A cross-sectional study. Medicina, 56.","DOI":"10.3390\/medicina56080383"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eaau3333","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer\u2019s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"Dominy","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/nan.12644","article-title":"Peripheral inflammation exacerbates \u03b1-synuclein toxicity and neuropathology in Parkinson\u2019s models","volume":"47","author":"Balducci","year":"2021","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1289\/ehp.1003013","article-title":"Neuroinflammation and \u03b1-synuclein dysfunction potentiate each other, driving chronic progression of neurodegeneration in a mouse model of Parkinson\u2019s disease","volume":"119","author":"Gao","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1159\/000477990","article-title":"A Role for Neuronal Alpha-Synuclein in Gastrointestinal Immunity","volume":"9","author":"Stolzenberg","year":"2017","journal-title":"J. Innate Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41531-022-00351-6","article-title":"Oral and gut dysbiosis leads to functional alterations in Parkinson\u2019s disease","volume":"8","author":"Jo","year":"2022","journal-title":"NPJ Park. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s41531-024-00705-2","article-title":"Ultrastructural localization of Porphyromonas gingivalis gingipains in the substantia nigra of Parkinson\u2019s disease brains","volume":"10","author":"Ermini","year":"2024","journal-title":"NPJ Park. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2471\/BLT.07.045120","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies","volume":"85","author":"Altman","year":"2007","journal-title":"Bull. World Health Organ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/jre.12007","article-title":"Gingival advanced glycation end-products in diabetes mellitus-associated chronic periodontitis: An immunohistochemical study","volume":"48","author":"Zizzi","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1902\/jop.2013.130092","article-title":"Resistin Levels in Gingival Crevicular Fluid of Patients With Chronic Periodontitis and Type 2 Diabetes Mellitus","volume":"85","author":"Gokhale","year":"2014","journal-title":"J. Periodontol."},{"key":"ref_32","unstructured":"(2011). International Standard Classification of Education: Education Programmes 2011. Standard No. ISCED-P 2011."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S159","DOI":"10.1002\/JPER.18-0006","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"89","author":"Tonetti","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1034\/j.1600-0765.2001.00011.x","article-title":"The dentogingival epithelial surface area revisited","volume":"36","author":"Hujoel","year":"2001","journal-title":"J. Periodontal Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/j.1600-051X.2008.01249.x","article-title":"Periodontal inflamed surface area: Quantifying inflammatory burden","volume":"35","author":"Nesse","year":"2008","journal-title":"J. Clin. Periodontol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1177\/1753425918796207","article-title":"Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype","volume":"24","author":"Liukkonen","year":"2018","journal-title":"Innate Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/jcpe.13290","article-title":"Treatment of stage I\u2013III periodontitis\u2014The EFP S3 level clinical practice guideline","volume":"47","author":"Sanz","year":"2020","journal-title":"J. Clin. Periodontol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1902\/jop.2016.160013","article-title":"Risk Indicators for Periodontitis in US Adults: NHANES 2009 to 2012","volume":"87","author":"Eke","year":"2016","journal-title":"J. Periodontol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15538","DOI":"10.1038\/s41598-019-52116-6","article-title":"Study of Periodontal Health in Almada-Seixal (SoPHiAS): A cross-sectional study in the Lisbon Metropolitan Area","volume":"9","author":"Botelho","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Machado, V., Aguilera, E.M., Botelho, J., Hussain, S.B., Leira, Y., Proen\u00e7a, L., D\u2019Aiuto, F., and Mendes, J.J. (2020). Association between Periodontitis and High Blood Pressure: Results from the Study of Periodontal Health in Almada-Seixal (SoPHiAS). J. Clin. Med., 9.","DOI":"10.3390\/jcm9051585"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1600-051X.2009.01382.x","article-title":"Heterogeneity of systemic inflammatory responses to periodontal therapy","volume":"36","author":"Behle","year":"2009","journal-title":"J. Clin. Periodontol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/cre2.162","article-title":"Systemic inflammatory burden and local inflammation in periodontitis: What is the link between inflammatory biomarkers in serum and gingival crevicular fluid?","volume":"5","author":"Zekeridou","year":"2019","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., and Kim, H.N. (2020). Changes in inflammatory cytokines in saliva after non-surgical periodontal therapy: A systematic review and meta-analysis. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18010194"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/12\/3586\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:01:03Z","timestamp":1760108463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/12\/3586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,19]]},"references-count":43,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["jcm13123586"],"URL":"https:\/\/doi.org\/10.3390\/jcm13123586","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,6,19]]}}}