The role of redox balance in cyanide toxicity and mitochondrial disease

氧化还原平衡在氰化物毒性和线粒体疾病中的作用

基本信息

  • 批准号:
    10782976
  • 负责人:
  • 金额:
    $ 3.73万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-01 至 2025-08-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY The electron transport chain (ETC) in the inner mitochondrial membrane is essential for efficient ATP production in the cell. ETC function can be disrupted both genetically and pharmacologically by mitochondrial diseases and metabolic poisons, respectively. Inefficient ATP production affects all tissues, but particularly the brain with its high energy demands, thus making this a deadly neurological problem. ETC dysfunction is often associated with buildup of the initial electron donor, NADH, within the mitochondria. This increase in NADH corresponds with a decrease in its oxidized form, NAD+, contributing to an overall NAD+/NADH ratio imbalance. Since NAD+ and NADH are cofactors for many redox reactions in the cell, this results in redox imbalance and reduced metabolic flux, intensifying the energy production problem. Cyanide, a pharmacological ETC inhibitor, and Leigh syndrome, a collection of fatal genetic mitochondrial diseases, both result in inefficient ATP production, NAD+/NADH ratio imbalances, and severe neurological consequences. Few cyanide antidotes exist, all of which have a limited efficacious time window for administration. No cure is available for any form of Leigh syndrome. We hypothesize that normalization of the NAD+/NADH ratio will improve outcomes for both cyanide poisoning and Leigh syndrome. Within Aim 1 of this proposal, we will investigate 1) if restoring NAD+/NADH ratio is sufficient for rescuing cyanide poisoning and 2) what occurs downstream of restoring NAD+/NADH ratio in the context of cyanide poisoning. Within Aim 2, we will determine if redox modulators can rescue disease phenotypes in an array of zebrafish models of Leigh syndrome designed to cover a wide breadth of mutations associated with Leigh syndrome. These disease phenotypes include glial reactivity and deficits in locomotion, oxygen consumption, and associative learning. Collectively, these experiments will evaluate the therapeutic value of restoring the NAD+/NADH ratio for different forms of mitochondrial dysfunction, and will focus on redox modulators that improve neurological outcomes.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Emily Tippetts其他文献

Emily Tippetts的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Emily Tippetts', 18)}}的其他基金

The role of redox balance in cyanide toxicity and mitochondrial disease
氧化还原平衡在氰化物毒性和线粒体疾病中的作用
  • 批准号:
    10536383
  • 财政年份:
    2022
  • 资助金额:
    $ 3.73万
  • 项目类别:

相似海外基金

Life outside institutions: histories of mental health aftercare 1900 - 1960
机构外的生活:1900 - 1960 年心理健康善后护理的历史
  • 批准号:
    DP240100640
  • 财政年份:
    2024
  • 资助金额:
    $ 3.73万
  • 项目类别:
    Discovery Projects
Development of a program to promote psychological independence support in the aftercare of children's homes
制定一项计划,促进儿童之家善后护理中的心理独立支持
  • 批准号:
    23K01889
  • 财政年份:
    2023
  • 资助金额:
    $ 3.73万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
  • 批准号:
    10452217
  • 财政年份:
    2022
  • 资助金额:
    $ 3.73万
  • 项目类别:
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
  • 批准号:
    10670838
  • 财政年份:
    2022
  • 资助金额:
    $ 3.73万
  • 项目类别:
Aftercare for young people: A sociological study of resource opportunities
年轻人的善后护理:资源机会的社会学研究
  • 批准号:
    DP200100492
  • 财政年份:
    2020
  • 资助金额:
    $ 3.73万
  • 项目类别:
    Discovery Projects
Creating a National Aftercare Strategy for Survivors of Pediatric Cancer
为小儿癌症幸存者制定国家善后护理策略
  • 批准号:
    407264
  • 财政年份:
    2019
  • 资助金额:
    $ 3.73万
  • 项目类别:
    Operating Grants
Aftercare of green infrastructure: creating algorithm for resolving human-bird conflicts
绿色基础设施的善后工作:创建解决人鸟冲突的算法
  • 批准号:
    18K18240
  • 财政年份:
    2018
  • 资助金额:
    $ 3.73万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Development of an aftercare model for children who have experienced invasive procedures
为经历过侵入性手术的儿童开发善后护理模型
  • 批准号:
    17K12379
  • 财政年份:
    2017
  • 资助金额:
    $ 3.73万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of a Comprehensive Aftercare Program for children's self-reliance support facility
为儿童自力更生支持设施制定综合善后护理计划
  • 批准号:
    17K13937
  • 财政年份:
    2017
  • 资助金额:
    $ 3.73万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Project#2 Extending Treatment Effects Through an Adaptive Aftercare Intervention
项目
  • 批准号:
    8742767
  • 财政年份:
    2014
  • 资助金额:
    $ 3.73万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了