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：
10041410
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 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10041410
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 Dr. 向国家老龄化研究所 (NIA) 提交的独立科学家奖 (K02) 申请。 Alexandru Movila 博士是一名早期研究员，目前是第三年的助理教授。他在诺瓦东南大学 (NSU) 的牙周病学系任职。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他的研究目前得到 R01AG064003、R03DE027153 的支持。和 R15DE28699 授予解决神经酰胺脂质诱发牙周炎相关的分子机制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此外，莫维拉博士的长期职业目标是成为一名领先的基础研究人员。目前，PI在衰老和阿尔茨海默病领域的研究非常有限。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因此，该职业发展 KO2 奖将为您提供受保护的时间。基于他在口腔发病机制和初步方面的现有专业知识，获得新研究领域的专业知识。结果，Movila 博士率先发现由关键牙周病原菌卟啉单胞菌产生的神经酰胺脂质 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蛋白前体蛋白的淀粉样变性加工该 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。了解阿尔茨海默病的病理进展，2) 接受实践培训以了解临床前的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资格。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。