Roles of Periodontal Bacteria-Derived Dihydroceramides in Alzheimer's Disease

牙周细菌衍生的二氢神经酰胺在阿尔茨海默病中的作用

• 批准号: 10591930
• 负责人: Alexandru Movila
• 金额: $ 13.65万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591930
• 关键词: Address; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Amyloid beta-42; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Apoptosis; Appointment; Award; Bacteria; Basic Science; Blood - brain barrier anatomy; Brain; C-terminal; Cells; Ceramides; Clinical; Clinical Trials; Collaborations; Dental Students; Doctor of Philosophy; Educational process of instructing; Experimental Models; Faculty; Florida; Foundations; Functional disorder; Future; Gingiva; Goals; Grant; Hippocampus (Brain); Human; In Vitro; Independent Scientist Award; Inflammation; Inflammatory; Injections; Innate Immune Response; Knowledge; Learning; Lesion; Lipids; Lipopolysaccharides; Mediating; Mentors; Modeling; Molecular; Molecular Weight; Mus; Names; National Institute of Dental and Craniofacial Research; National Institute on Aging; Neurodegenerative Disorders; Neurofibrillary Tangles; Oral; Pathogenesis; Pathogenicity; Pathologic; Patients; Peptide Hydrolases; Periodontal Diseases; Periodontitis; Permeability; Porphyromonas; Porphyromonas gingivalis; Production; Publications; Publishing; Reporting; Research; Research Personnel; Risk Factors; Role; Scientist; Signal Transduction; Testing; Time; Tissues; Training; Universities; Virulence Factors; Virulent; Wild Type Mouse; Workload; age related; amyloid pathology; amyloid precursor protein processing; amyloidogenesis; base; career; career development; cytokine; dihydroceramide; experience; frontal lobe; gingipain; human tissue; improved; in vivo; interest; mid-career faculty; mouse model; neuroimmunology; neuropathology; novel; novel therapeutic intervention; oral bacteria; oral biology; oral immunology; oral pathogen; periodontopathogen; pre-clinical; professor; research study; skills; tau Proteins; tau aggregation; tau phosphorylation; undergraduate student

ABSTRACT This is an Independent Scientist Award (K02) application to the National Institute on Aging (NIA) from Dr. Alexandru Movila, Ph.D. who is an earlier stage investigator. Dr. Movila is an Assistant Professor in his third year appointment in the Department of Periodontology at Nova Southeastern University (NSU). Throughout his faculty career, Dr. Movila has established a strong publication record as an independent investigator in the field of oral inflammation induced by oral pathogens. His research is currently supported by R01AG064003, R03DE027153, and R15DE28699 grants addressing molecular mechanisms of ceramide lipids-induced periodontitis in relation to aging. Because the emerging evidence indicates that virulence factors secreted by periodontal pathogens may be engaged in initiation and/or progression of Alzheimer’s disease, the scientific goal of Dr. Movila is to establish a foundation of research for elucidation of pathogenic engagement of periodontal disease in the onset and progression of Alzheimer’s disease. Further, Dr. Movila’s long-term career goal is to become a leading basic research scientist in the field of aging and Alzheimer’s disease research. Currently, the PI has very limited experience in the pathophysiology of age-dependent neurodegenerative disease, including Alzheimer’s disease. However, due to the current workload at NSU that involve teaching and research mentoring of undergraduate and graduate dental students, he can only allocate a limited time for the research on Alzheimer’s disease associated with periodontitis. Thus, this career development KO2 award would provide the protected time to gain expertise in a new field of research. Based on his existing expertise in the oral pathogenesis and preliminary results, Dr. Movila hypothesized that ceramide lipid produced by the key periodontal pathogen Porphyromonas gingvalis, is engaged in Alzheimer’s disease pathogenesis via elevation of the hyper-phosphorylation of tau and amyloidogenic processing of amyloid precursor protein. The primary career development goals of this K02 application are: 1) to identify the possible pathogenic factors produced by periodontal pathogens that promotes progression of the Alzheimer’s disease pathology, 2) to receive hands-on training to learn the pre-clinical experimental mouse models of Alzheimer’s disease, 3) to establish academic collaborations with distinguished researchers in the fields; and 4) to build up academic credential in the Alzheimer disease research. The proposed career development training and research studies will help to Dr. Movila not only improving his knowledge and skill to study Alzheimer’s disease, but also increasing the network for collaborations and reputation in the field.

抽象的 这是 Dr. 向国家老龄化研究所 (NIA) 提交的独立科学家奖 (K02) 申请。 亚历山德鲁·莫维拉博士谁是早期调查员。 Movila 博士是助理教授，第三年 受聘于诺瓦东南大学 (NSU) 牙周病学系。在他的整个师资队伍中 职业生涯中，莫维拉博士作为口腔领域的独立研究者建立了良好的发表记录 口腔病原体引起的炎症。他的研究目前得到 R01AG064003、R03DE027153、 和 R15DE28699 授予解决神经酰胺脂质诱发牙周炎相关的分子机制 到老化。因为新出现的证据表明牙周病原体分泌的毒力因子 可能参与阿尔茨海默病的发生和/或进展，Movila 博士的科学目标是 为阐明牙周病发病时的致病参与奠定研究基础 和阿尔茨海默病的进展。此外，Movila 博士的长期职业目标是成为领先的基础 衰老和阿尔茨海默病研究领域的研究科学家。目前，PI 的能力非常有限 在年龄依赖性神经退行性疾病（包括阿尔茨海默病）的病理生理学方面拥有丰富的经验。 然而，由于 NSU 目前的工作量涉及本科生的教学和研究指导 和牙科研究生一样，他只能分配有限的时间进行阿尔茨海默病的研究 与牙周炎有关。因此，这个职业发展 KO2 奖项将为 获得新研究领域的专业知识。基于他现有的口腔发病机制专业知识和初步研究 结果，Movila 博士推测，神经酰胺脂质是由关键牙周病原菌卟啉单胞菌产生的 gingvalis 通过提高 tau 蛋白的过度磷酸化参与阿尔茨海默病的发病机制 淀粉样前体蛋白的淀粉样变加工。 K02的主要职业发展目标 应用有： 1）鉴定牙周病原菌产生的可能致病因素，促进牙周病的发生。 阿尔茨海默病病理学的进展，2) 接受实践培训以学习临床前知识 阿尔茨海默病的实验小鼠模型，3) 与杰出人士建立学术合作 该领域的研究人员； 4) 建立阿尔茨海默病研究的学术证书。拟议的 职业发展培训和研究将帮助 Movila 博士不仅提高他的知识， 研究阿尔茨海默病的技能，同时也扩大了该领域的合作网络和声誉。