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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.

摘要