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Role of vascular KATP channels in Alzheimer’s neurodegeneration and dementia

血管 KATP 通道在阿尔茨海默氏症神经变性和痴呆中的作用

基本信息

批准号：
10713794
负责人：
Colin G Nichols
金额：
$ 38.96万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10713794
关键词：
ABCC9 gene Acute Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease risk Amyloid beta-Protein Amyloid deposition Animal Model Animals Blood Vessels Blood capillaries Blood flow Brain CRSP3 gene Cantu syndrome Cardiovascular system Cause of Death Cerebrovascular Circulation Cerebrovascular Disorders Cerebrovascular system Collection Complex Data Dementia Deposition Development Diameter Disease Progression Dominant-Negative Mutation Elderly Electrophysiology (science)Endothelial Cells Exhibits Family member Future Genes Glyburide Goals Hippocampus Human Individual Ion Channel Knock-in Knock-in Mouse Knock-out Link Measurement Modeling Mus Mutation Nerve Degeneration Neurons Nutrient Oxygen Pathogenesis Pathology Patients Pericytes Pinacidil Placebos Potassium Potassium Channel Regulation Reporting Role Series Smooth Muscle Myocytes Testing Tissues Toxic effect Vascular Smooth Muscle Vascular remodeling Visual impairment Width Work cell type cerebral amyloidosis cerebral artery dementia risk experimental study gain of function gain of function mutation gene product genetic manipulation hemodynamics loss of function mutation mind control mouse model neurovascular neurovascular coupling novel therapeutics pharmacologic response sulfonylurea receptor targeted agent tau Proteins tool

项目摘要

Abstract A major focus of our efforts is to understand the mechanistic basis and functional consequences of ATPsensitive potassium (KATP) ion channels in the cardiovascular system. There are contradictory reports of KATP channel involvement in Alzheimer's Disease (AD) pathogenesis, and we hypothesize that this is because of the involvement of different channels in neurons versus in cerebral blood vessels. We propose that blocking KATP channels in blood vessels specifically will be beneficial, and we propose to test this in AD model mice by precise genetic manipulation of cardiovascular KATP channels. If successful, these studies will form the background to the testing of relevant pharmacological approaches to CS therapy in animal models and in humans, with the ultimate goal of developing a specific therapy for CS and related pathologies.

抽象的我们努力的一个主要重点是了解其机制基础和功能后果心血管系统中的 ATP 敏感钾 (KATP) 离子通道。有相互矛盾的报道 KATP 通道参与阿尔茨海默病 (AD) 发病机制，我们推测这是因为神经元与脑血管中涉及的通道不同。我们建议阻断血管中的 KATP 通道将是有益的，我们建议在 AD 中进行测试通过心血管 KATP 通道的精确基因操作建立模型小鼠。如果成功的话，这些研究将为在动物模型中测试 CS 治疗的相关药理学方法提供背景在人类中，最终目标是开发针对 CS 和相关病理的特定疗法。

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pore-forming transmembrane domains control ion selectivity and selectivity filter conformation in the KirBac1.1 potassium channel.

DOI：
10.1085/jgp.202012683
发表时间：
2021-05-03
期刊：
The Journal of general physiology
影响因子：
0
作者：
Matamoros M;Nichols CG
通讯作者：
Nichols CG

Coronavirus Proteins as Ion Channels: Current and Potential Research.

DOI：
10.3389/fimmu.2020.573339
发表时间：
2020
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
McClenaghan C;Hanson A;Lee SJ;Nichols CG
通讯作者：
Nichols CG

Transient Notch Activation Induces Long-Term Gene Expression Changes Leading to Sick Sinus Syndrome in Mice.

瞬态缺口激活诱导长期基因表达变化，导致小鼠病态的窦综合征。

DOI：
10.1161/circresaha.116.310396
发表时间：
2017-08-18
期刊：
Circulation research
影响因子：
20.1
作者：
Qiao Y;Lipovsky C;Hicks S;Bhatnagar S;Li G;Khandekar A;Guzy R;Woo KV;Nichols CG;Efimov IR;Rentschler S
通讯作者：
Rentschler S

Sulfonylurea-Insensitive Permanent Neonatal Diabetes Caused by a Severe Gain-of-Function Tyr330His Substitution in Kir6.2.

DOI：
10.1159/000521858
发表时间：
2022
期刊：
Hormone research in paediatrics
影响因子：
3.2
作者：
通讯作者：

The T1-tetramerisation domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac sodium channel.

DOI：
10.1002/1873-3468.14279
发表时间：
2022-03
期刊：
FEBS LETTERS
影响因子：
3.5
作者：
D'Avanzo, Nazzareno;Miles, Andrew J.;Powl, Andrew M.;Nichols, Colin G.;Wallace, B. A.;O'Reilly, Andrias O.
通讯作者：
O'Reilly, Andrias O.