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The roles of neuronal primary cilia in Alzheimer's disease

神经元初级纤毛在阿尔茨海默病中的作用

基本信息

批准号：
10285814
负责人：
Amal Alachkar
金额：
$ 37.58万
依托单位：
CHAPMAN 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：
2020-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10285814
关键词：
3xTg-AD mouse Adenylate Cyclase Administrative Supplement Agonist Alzheimer&apos s Disease Alzheimer&apos s disease model Animals Antibodies Arl proteins Axonal Transport Behavioral Behavioral Assay Brain Brain region California Cardiovascular Diseases Cell division Cell surface Cells Cilia Cognitive deficits Defect Dementia Dependovirus Disease Disease Progression Dopamine Receptor Drug Delivery Systems Drug Targeting Enterobacteria phage P1 Cre recombinase Fenoldopam Functional disorder Genes Genetic Genetic Engineering Goals Hippocampus (Brain)Immunohistochemistry Impaired cognition Injections Institution Kidney Diseases Knockout Mice Knowledge Laboratories Learning Length Liver diseases LoxP-flanked allele MAPT gene Measures Memory Memory impairment Microtubule Bundle Microtubules Mus Mutation Nerve Degeneration Neurodegenerative Disorders Neuroglia Neurologic Deficit Neurons Organelles Outcome Pathogenesis Pharmacology Physiology Play Prefrontal Cortex Records Research Role Sensory Serotyping Signal Transduction Site Structure Testing Transgenes Universities ciliopathy improved mouse model mutant nanoparticle drug neurotransmission targeted treatment

项目摘要

Project Abstract Primary cilia are mechano- and chemo-sensory organelles with diverse functions. Abnormal function or structure of primary cilia cause a list of diseases, termed ciliopathies. Although ciliopathies include expanding spectrum of kidney, liver, and cardiovascular disorders, it is yet to be investigated whether or not cilia are associated with Alzheimer’s disease (AD) and/or its related dementias. In this Administrative Supplement proposal, we combine expertise from two laboratories of the neighboring institutions. This multi-PI proposal includes Dr. Amal Alachkar (the University of California, Irvine), whose research group has strong expertise in neurological degeneration including Alzheimer, and Dr. Surya Nauli (Chapman University), whose laboratory has strong records in interrogating primary cilia functions. The overall goal of this proposal is to examine the alterations of cilia structure and functions in early- and late-stage AD in 3xTg mice brains. The role of cilia will also be evaluated using conditional inducible IFT88 knockout mice that do not possess cilia. IFT88 mouse will be put into the 3xTg-AD mouse background. Our first aim is therefore to test the hypothesis that cilia structure/length is altered in early- and/or late-stage 3xTg-AD mice. The second aim is to test the hypothesis that genetic and pharmacological manipulations of cilia alter behavioral changes in AD. The outcomes of these limited studies offer new knowledge if genetic elimination of cilia exacerbates behavioral deficits in 3xTg-AD mouse and if cilia-targeted therapy improves the behavioral deficits in 3xTg-AD mice.

项目摘要