{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:10:03Z","timestamp":1790878203248,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Program for Overseas Students in Sichuan Province","award":["2021-29-1"],"award-info":[{"award-number":["2021-29-1"]}]},{"name":"Science and Technology Program for Overseas Students in Sichuan Province","award":["2021YFSY0011"],"award-info":[{"award-number":["2021YFSY0011"]}]},{"name":"Science and Technology Program for Overseas Students in Sichuan Province","award":["2022NSFSC1359"],"award-info":[{"award-number":["2022NSFSC1359"]}]},{"name":"Science and Technology Program for Overseas Students in Sichuan Province","award":["RCDWJS2021-16"],"award-info":[{"award-number":["RCDWJS2021-16"]}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2021-29-1"],"award-info":[{"award-number":["2021-29-1"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2021YFSY0011"],"award-info":[{"award-number":["2021YFSY0011"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2022NSFSC1359"],"award-info":[{"award-number":["2022NSFSC1359"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["RCDWJS2021-16"],"award-info":[{"award-number":["RCDWJS2021-16"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Funding from West China Hospital of Stomatology Sichuan University","award":["2021-29-1"],"award-info":[{"award-number":["2021-29-1"]}]},{"name":"Research Funding from West China Hospital of Stomatology Sichuan University","award":["2021YFSY0011"],"award-info":[{"award-number":["2021YFSY0011"]}]},{"name":"Research Funding from West China Hospital of Stomatology Sichuan University","award":["2022NSFSC1359"],"award-info":[{"award-number":["2022NSFSC1359"]}]},{"name":"Research Funding from West China Hospital of Stomatology Sichuan University","award":["RCDWJS2021-16"],"award-info":[{"award-number":["RCDWJS2021-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Neuronal apoptosis is a major contributor to Alzheimer\u2019s disease (AD). Periodontitis is a significant risk factor for AD. The periodontal pathogens Porphyromonas gingivalis and Treponema denticola have been shown to initiate the hallmark pathologies and behavioral symptoms of AD. Studies have found that T. denticola infection induced Tau hyperphosphorylation and amyloid \u03b2 accumulation in the hippocampi of mice. A\u03b2 accumulation is closely associated with neuronal apoptosis. However, the roles of T. denticola in neuronal apoptosis remain unclear and its roles in AD pathology need further study. Objective: This study aimed to investigate whether oral infection with T. denticola induced alveolar bone loss and neuronal apoptosis in mice. Methods: C57BL\/6 mice were orally administered with T. denticola, Micro-CT was employed to assess the alveolar bone resorption. Western blotting, quantitative PCR, and TUNEL staining were utilized to detect the apoptosis-associated changes in mouse hippocampi. N2a were co-cultured with T. denticola to verify in vivo results. Results: Mice infected with T. denticola exhibited more alveolar bone loss compared with the control mice. T. denticola oral infection induced neuronal apoptosis in hippocampi of mice. Consistent results of the apoptosis-associated protein expression were observed in N2a cells treated with T. denticola and A\u03b21\u201342 in vitro. However, the A\u03b2 inhibitor reversed these results, suggesting that A\u03b21\u201342 mediates T. denticola infection-induced neuronal apoptosis. Conclusions: This study found that oral infected T. denticola caused alveolar bone loss, and induced neuronal apoptosis by promoting A\u03b2 accumulation in mice, providing evidence for the link between periodontitis and AD.<\/jats:p>","DOI":"10.3390\/pathogens11101150","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T01:21:07Z","timestamp":1665364867000},"page":"1150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Treponema denticola Induces Neuronal Apoptosis by Promoting Amyloid-\u03b2 Accumulation in Mice"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5021-454X","authenticated-orcid":false,"given":"Linrui","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Geriatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Oral Mucosal Diseases, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Jian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Geriatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Geriatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqun","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Geriatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkun","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Geriatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neuron.2006.09.016","article-title":"A hundred years of Alzheimer\u2019s disease research","volume":"52","author":"Hardy","year":"2006","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1474-4422(18)30403-4","article-title":"Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Collaborators","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1038\/d41586-018-05717-6","article-title":"Alzheimer\u2019s disease","volume":"559","author":"Hodson","year":"2018","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","article-title":"Alzheimer\u2019s disease","volume":"388","author":"Scheltens","year":"2016","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1038\/cdd.2015.16","article-title":"Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation","volume":"22","author":"Kaushal","year":"2015","journal-title":"Cell Death Differ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12221","article-title":"Periodontitis: Facts, fallacies and the future","volume":"75","author":"Slots","year":"2017","journal-title":"Periodontol 2000"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12979-017-0110-7","article-title":"Porphyromonas gingivalis, a periodontitis causing bacterium, induces memory impairment and age-dependent neuroinflammation in mice","volume":"15","author":"Ding","year":"2018","journal-title":"Immun. Ageing"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ide, M., Harris, M., Stevens, A., Sussams, R., Hopkins, V., Culliford, D., Fuller, J., Ibbett, P., Raybould, R., and Thomas, R. (2016). Periodontitis and Cognitive Decline in Alzheimer\u2019s Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151081"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jalz.2007.08.004","article-title":"Inflammation and Alzheimer\u2019s disease: Possible role of periodontal diseases","volume":"4","author":"Kamer","year":"2008","journal-title":"Alzheimers Dement."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/prd.12327","article-title":"Periodontal disease as a possible cause for Alzheimer\u2019s disease","volume":"83","author":"Kamer","year":"2020","journal-title":"Periodontol 2000"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/jre.12623","article-title":"Periodontitis, periodontal inflammation, and mild cognitive impairment: A 5-year cohort study","volume":"54","author":"Iwasaki","year":"2019","journal-title":"J. Periodontal Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.neurobiolaging.2014.10.038","article-title":"Periodontal disease associates with higher brain amyloid load in normal elderly","volume":"36","author":"Kamer","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","unstructured":"Ilievski, V., Zuchowska, P.K., Green, S.J., Toth, P.T., Ragozzino, M.E., Le, K., Aljewari, H.W., O\u2019Brien-Simpson, N., Reynolds, E.C., and Watanabe, K. (2018). Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204941"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s12031-020-01629-1","article-title":"Effects of Porphyromonas gingivalis and Its Underlying Mechanisms on Alzheimer-Like Tau Hyperphosphorylation in Sprague-Dawley Rats","volume":"71","author":"Tang","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10117","DOI":"10.18632\/aging.103306","article-title":"Salvianolic Acid B improves cognitive impairment by inhibiting neuroinflammation and decreasing Abeta level in Porphyromonas gingivalis-infected mice","volume":"12","author":"Liu","year":"2020","journal-title":"Aging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1097\/00001756-199307000-00002","article-title":"Alzheimer\u2019s disease\u2014A spirochetosis?","volume":"4","author":"Miklossy","year":"1993","journal-title":"Neuroreport"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/1742-2094-8-90","article-title":"Alzheimer\u2019s disease\u2014A neurospirochetosis. Analysis of the evidence following Koch\u2019s and Hill\u2019s criteria","volume":"8","author":"Miklossy","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1046\/j.0902-0055.2001.00100.x","article-title":"Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer\u2019s disease","volume":"17","author":"Riviere","year":"2002","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1007\/s12031-021-01827-5","article-title":"Oral Treponema denticola Infection Induces A\u03b21\u201340 and A\u03b21\u201342 Accumulation in the Hippocampus of C57BL\/6 Mice","volume":"71","author":"Su","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1177\/00220345221076772","article-title":"Treponema denticola Induces Alzheimer-Like Tau Hyperphosphorylation by Activating Hippocampal Neuroinflammation in Mice","volume":"101","author":"Tang","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2003.12.005","article-title":"Cell cycle regulation of neuronal apoptosis in development and disease","volume":"72","author":"Becker","year":"2004","journal-title":"Prog. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S187","DOI":"10.1016\/0197-4580(94)90202-X","article-title":"Possible role of neuronal apoptosis in Alzheimer\u2019s disease","volume":"15","author":"Johnson","year":"1994","journal-title":"Neurobiol. Aging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.3233\/JAD-171133","article-title":"Alzheimer\u2019s Amyloid-beta is an Antimicrobial Peptide: A Review of the Evidence","volume":"62","author":"Gosztyla","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1080\/14728222.2019.1702972","article-title":"Emerging roles of N- and C-terminally truncated A\u03b2 species in Alzheimer\u2019s disease","volume":"23","author":"Wirths","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11532","DOI":"10.1038\/s41598-017-09996-3","article-title":"Cofilin-mediated Neuronal Apoptosis via p53 Translocation and PLD1 Regulation","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.nbd.2012.11.006","article-title":"Age-dependent alterations in the presynaptic active zone in a Drosophila model of Alzheimer\u2019s disease","volume":"51","author":"Huang","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_28","first-page":"5","article-title":"Amyloid-beta Alzheimer targets\u2014protein processing, lipid rafts, and amyloid-beta pores","volume":"89","author":"Arbor","year":"2016","journal-title":"Yale J. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature04533","article-title":"A specific amyloid-\u03b2 protein assembly in the brain impairs memory","volume":"440","author":"Koh","year":"2006","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1084\/jem.17.2.232","article-title":"A Demonstration of Treponema Pallidum in the Brain in Cases of General Paralysis","volume":"17","author":"Noguchi","year":"1913","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jalz.2006.01.002","article-title":"Potentially modifiable risk factors for dementia in identical twins","volume":"2","author":"Gatz","year":"2006","journal-title":"Alzheimers Dement."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"475S","DOI":"10.1093\/ajcn\/83.2.475S","article-title":"Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging","volume":"83","author":"Kornman","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3233\/JAD-210429","article-title":"A Novel Approach to the Treatment and Prevention of Alzheimer\u2019s Disease Based on the Pathology and Microbiology","volume":"84","author":"Allen","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1097\/00001756-199412000-00031","article-title":"Immunohistochemical evidence for apoptosis in Alzheimer\u2019s disease","volume":"5","author":"Su","year":"1994","journal-title":"Neuroreport"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1097\/00005072-199708000-00007","article-title":"DNA damage distribution in the human brain as shown by in situ end labeling; area-specific differences in aging and Alzheimer disease in the absence of apoptotic morphology","volume":"56","author":"Lucassen","year":"1997","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1007\/s11064-014-1454-4","article-title":"Apoptosis in Alzheimer\u2019s disease: An understanding of the physiology, pathology and therapeutic avenues","volume":"39","author":"Obulesu","year":"2014","journal-title":"Neurochem. Res."},{"key":"ref_37","first-page":"125","article-title":"Markers of apoptosis and models of programmed cell death in Alzheimer\u2019s disease","volume":"59","author":"Hugon","year":"2000","journal-title":"J. Neural. Transm. Suppl."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1097\/00005072-199811000-00007","article-title":"Caspase dependent DNA fragmentation might be associated with excitotoxicity in Alzheimer disease","volume":"57","author":"Masliah","year":"1998","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/cdd.2013.153","article-title":"The rheostat in the membrane: BCL-2 family proteins and apoptosis","volume":"21","author":"Volkmann","year":"2014","journal-title":"Cell Death Differ"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9700","DOI":"10.1038\/s41598-019-45915-4","article-title":"Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis","volume":"9","author":"Zaitoun","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/j.1471-4159.2004.02416.x","article-title":"Neuroprotective properties of Bcl-w in Alzheimer disease","volume":"89","author":"Zhu","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/s41419-020-2417-0","article-title":"BCL-w: Apoptotic and non-apoptotic role in health and disease","volume":"11","author":"Hartman","year":"2020","journal-title":"Cell Death Dis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neuroscience.2007.08.021","article-title":"Time-course of c-Jun N-terminal kinase activation after cerebral ischemia and effect of D-JNKI1 on c-Jun and caspase-3 activation","volume":"150","author":"Repici","year":"2007","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1111\/j.1460-9568.2010.07158.x","article-title":"c-Jun N-terminal kinase signaling pathway in excitotoxic cell death following kainic acid-induced status epilepticus","volume":"31","author":"Spigolon","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1046\/j.1474-9728.2002.00014.x","article-title":"The true face of JNK activation in apoptosis","volume":"1","author":"Lin","year":"2002","journal-title":"Aging Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1523\/JNEUROSCI.4736-04.2005","article-title":"Beta-amyloid-induced neuronal apoptosis involves c-Jun N-terminal kinase-dependent downregulation of Bcl-w","volume":"25","author":"Yao","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"28294","DOI":"10.1074\/jbc.M212265200","article-title":"Neurotoxic mechanisms caused by the Alzheimer\u2019s disease-linked Swedish amyloid precursor protein mutation: Oxidative stress, caspases, and the JNK pathway","volume":"278","author":"Marques","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1111\/j.1460-9568.2008.06258.x","article-title":"Active c-jun N-terminal kinase induces caspase cleavage of tau and additional phosphorylation by GSK-3beta is required for tau aggregation","volume":"27","author":"Sahara","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.ceb.2009.09.004","article-title":"Mitochondrial cell death effectors","volume":"21","author":"Brenner","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1093\/emboj\/20.23.6627","article-title":"Apoptosis-associated release of Smac\/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2","volume":"20","author":"Adrain","year":"2001","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1111\/j.1460-9568.2004.03554.x","article-title":"Dynamic changes of the anti- and pro-apoptotic proteins Bcl-w, Bcl-2, and Bax with Smac\/Diablo mitochondrial release after photothrombotic ring stroke in rats","volume":"20","author":"Hu","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/nm0997-1016","article-title":"Distinct sites of intracellular production for Alzheimer\u2019s disease A beta40\/42 amyloid peptides","volume":"3","author":"Hartmann","year":"1997","journal-title":"Nat. Med."},{"key":"ref_53","first-page":"e12000","article-title":"Classifying dementia progression using microbial profiling of saliva","volume":"12","author":"Bathini","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"951","DOI":"10.3233\/JAD-131037","article-title":"Pathogen-free husbandry conditions alleviate behavioral deficits and neurodegeneration in AD10 anti-NGF mice","volume":"38","author":"Tzanoulinou","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1532-5415.2004.52109.x","article-title":"A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer\u2019s disease","volume":"52","author":"Loeb","year":"2004","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"117043","DOI":"10.1016\/j.lfs.2019.117043","article-title":"Amentoflavone suppresses amyloid beta1-42 neurotoxicity in Alzheimer\u2019s disease through the inhibition of pyroptosis","volume":"239","author":"Zhao","year":"2019","journal-title":"Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0924-977X(97)00069-2","article-title":"Neuroprotective role of S12024 against neurodegeneration in the rat dentate gyrus","volume":"8","author":"Vecino","year":"1998","journal-title":"Eur Neuropsychopharmacol"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00401-015-1386-3","article-title":"Amyloid beta oligomers in Alzheimer\u2019s disease pathogenesis, treatment, and diagnosis","volume":"129","author":"Viola","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1111\/j.1742-4658.2009.07094.x","article-title":"Overexpression of Tfam protects mitochondria against beta-amyloid-induced oxidative damage in SH-SY5Y cells","volume":"276","author":"Xu","year":"2009","journal-title":"FEBS J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1016\/j.cellsig.2007.04.005","article-title":"Opposing effects of Bad phosphorylation at two distinct sites by Akt1 and JNK1\/2 on ischemic brain injury","volume":"19","author":"Wang","year":"2007","journal-title":"Cell Signal"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/j.freeradbiomed.2006.08.015","article-title":"Protection by EGb 761 against beta-amyloid-induced neurotoxicity: Involvement of NF-kappaB, SIRT1, and MAPKs pathways and inhibition of amyloid fibril formation","volume":"41","author":"Longpre","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1128\/IAI.06098-11","article-title":"E-selectin mediates Porphyromonas gingivalis adherence to human endothelial cells","volume":"80","author":"Komatsu","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1902\/jop.2011.110406","article-title":"Role of p38 mitogen-activated protein kinase pathway in Porphyromonas gingivalis lipopolysaccharide-induced VCAM-1 expression in human aortic endothelial cells","volume":"83","author":"Liu","year":"2012","journal-title":"J. Periodontol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1111\/jnc.15096","article-title":"Receptor for advanced glycation end products up-regulation in cerebral endothelial cells mediates cerebrovascular-related amyloid beta accumulation after Porphyromonas gingivalis infection","volume":"158","author":"Zeng","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"957","DOI":"10.3233\/JAD-215103","article-title":"Do Periodontal Pathogens or Associated Virulence Factors Have a Deleterious Effect on the Blood-Brain Barrier, Contributing to Alzheimer\u2019s Disease?","volume":"85","author":"Kouki","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3758\/BRM.41.4.1149","article-title":"Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses","volume":"41","author":"Faul","year":"2009","journal-title":"Behav. Res. Methods"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Rivera, M.F., Chukkapalli, S.S., Velsko, I.M., Lee, J.-Y., Bhattacharyya, I., Dolce, C., Toro, E.J., Holliday, S., and Kesavalu, L. (2014). Bis-enoxacin blocks rat alveolar bone resorption from experimental periodontitis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092119"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/andr.12334","article-title":"Inter- and intra-laboratory standardization of TUNEL assay for assessment of sperm DNA fragmentation","volume":"5","author":"Ribeiro","year":"2017","journal-title":"Andrology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.119.3.493","article-title":"Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation","volume":"119","author":"Gavrieli","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/10\/1150\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:59Z","timestamp":1760143619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/10\/1150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":70,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["pathogens11101150"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11101150","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]}}}