Role 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

基本信息

批准号：
10227124
负责人：
Alexandru Movila
金额：
$ 13.65万
依托单位：
NOVA SOUTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2021-12-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10227124
关键词：
Address Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos 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

项目摘要

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.

抽象的这是向美国国家老化研究所（NIA）的独立科学家奖（K02）申请。 Alexandru Movila博士谁是较早的舞台调查员。 Movila博士是第三年的助理教授在Nova Southeastern University（NSU）牙周病学系任命。通过他的教师职业生涯，Movila博士在口头领域建立了庞大的出版记录口腔病原体引起的炎症。他的研究目前得到R01AG064003，R03DE027153的支持 R15DE28699赠款，涉及神经酰胺脂质诱导的牙周炎的分子机制衰老。因为新兴的证据表明牙周病原体分泌的病毒因素可能从事阿尔茨海默氏病的启动和/或进展，Movila博士的科学目标是为阐明牙周疾病的致病性参与的研究基础和阿尔茨海默氏病的进展。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氏病研究领域的研究科学家。目前，PI非常有限在依赖年龄的神经退行性疾病（包括阿尔茨海默氏病）病理生理学的经验。但是，由于当前在NSU的工作量涉及本科教学和研究心理和研究生牙科学生，他只能分配有限的时间来研究阿尔茨海默氏病与牙周炎有关。那就是这一职业发展KO2奖将为受保护的时间提供在新的研究领域中获得专业知识。基于他在口腔发病机理和初步的现有专业知识结果，Movila博士假设由关键牙周病原体卟啉症产生的神经酰胺脂质金瓦利斯（Gingvalis）通过升高tau的高磷酸化和淀粉样蛋白前体蛋白的淀粉样生成加工。这个K02的主要职业发展目标应用是：1）确定促进的牙周病原体产生的可能的病原因子阿尔茨海默氏病病理学的进展，2）接受动手培训以学习临床前阿尔茨海默氏病的实验小鼠模型，3）建立具有杰出的学术合作领域的研究人员； 4）在阿尔茨海默氏病研究中建立学术证书。提议职业发展培训和研究研究将有助于Movila博士不仅提高他的知识和研究阿尔茨海默氏病的技巧，同时也提高了该领域的合作和声誉的网络。