Role of periodontal bacteria-derived dihydroceramides in Alzheimer's disease

摘要 这是独立科学家奖(K02)向国家老龄研究所(NIA)的申请。 Alexandru Movila博士，他是一名早期的调查员。莫维拉博士是一名三年级的助理教授 被任命为诺瓦东南大学牙周病学系。在他的教职员工中 作为口腔领域的独立研究员，莫维拉博士在口腔领域建立了良好的发表记录 由口腔病原体引起的炎症。他的研究目前得到了R01AG064003、R03DE027153、 和R15DE28699研究神经酰胺脂诱导牙周炎的分子机制 为衰老干杯。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启动和/或进展，莫维拉博士的科学目标是 为阐明牙周病发病的致病机制奠定基础 以及阿尔茨海默氏症的进展。此外，莫维拉博士的长期职业目标是成为领先的基础 老龄化和阿尔茨海默氏症研究领域的研究科学家。目前，PI的规模非常有限 有老年性神经退行性疾病(包括阿尔茨海默病)的病理生理学经验。 然而，由于目前南洋师范大学的工作量涉及本科生的教学和研究辅导 和牙科研究生，他只能分配有限的时间用于阿尔茨海默病的研究 与牙周炎有关。因此，这项职业发展KO2奖将提供保护时间 在一个新的研究领域获得专业知识。根据他现有的口腔发病机制和初步的专业知识 结果，莫维拉博士假设牙周关键致病菌--卟啉单胞菌所产生的神经酰胺类脂 Gingvalis通过上调tau和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变性加工。K02的主要职业发展目标 应用：1)确定牙周致病菌可能产生的致病因素，促进 阿尔茨海默病的病理进展，2)接受实践培训，学习临床前 阿尔茨海默病实验小鼠模型，3)与杰出人士建立学术合作 4)建立阿尔茨海默病研究的学术资历。建议数 职业发展培训和研究研究将有助于莫维拉博士不仅提高他的知识和 研究阿尔茨海默氏症的技能，但也增加了合作网络和该领域的声誉。

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.