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

摘要 这是一个独立的科学家奖（K 02）的应用程序，国家研究所对老龄化（NIA）博士。 Alexandru Movila博士他是一名早期调查员莫维拉博士是助理教授在他的第三年 2009年，他被任命为诺瓦东南大学牙周病学系（NSU）的副教授。在他的整个系里 在职业生涯中，Movila博士作为口腔领域的独立研究者建立了良好的出版记录 由口腔病原体引起的炎症。他的研究目前得到R 01 AG 064003、R 03 DE 027153的支持， 和R15 DE 28699赠款解决神经酰胺脂质诱导的牙周炎的分子机制， 变老因为越来越多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启动和/或进展，Movila博士的科学目标是 为阐明牙周病发病过程中的致病因素奠定研究基础 和阿尔茨海默病的发展此外，莫维拉博士的长期职业目标是成为一个领先的基本 老年痴呆症研究领域的研究科学家。目前，PI拥有的 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， 和研究生牙科学生，他只能分配有限的时间对阿尔茨海默氏症的研究 与牙周炎有关。因此，这一职业发展KO 2奖将提供受保护的时间， 在新的研究领域获得专业知识。根据他在口腔发病机制方面的现有专业知识和初步的 结果，莫维拉博士假设，神经酰胺脂质产生的关键牙周病原体卟啉单胞菌 gingvalis通过升高tau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形成加工。本K 02的主要职业发展目标 应用是：1）确定可能的致病因素产生的牙周病原体，促进 阿尔茨海默病的病理学进展，2）接受实践培训，学习临床前 阿尔茨海默病的实验小鼠模型，3）与杰出的学术合作伙伴建立学术合作关系， 4）建立阿尔茨海默病研究的学术资格。拟议 职业发展培训和研究学习将有助于莫维拉博士不仅提高他的知识， 研究阿尔茨海默病的技能，而且还增加了该领域的合作网络和声誉。

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.