CAM Antioxidants and ALS
CAM 抗氧化剂和 ALS
基本信息
- 批准号:7902742
- 负责人:
- 金额:$ 30.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-06-01 至 2013-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylcarnitineAdoptedAffectAgeAgingAlzheimer&aposs DiseaseAmericanAmerican Cancer SocietyAnimal ModelAnimalsAntioxidantsAstrocytesBiological AssayBrainCaviaCell Culture TechniquesCessation of lifeChelation TherapyChronicChronic DiseaseClinical ResearchCollaborationsCommunitiesComplementary and alternative medicineDevelopmentDiseaseDisease ProgressionDisease modelEmployee StrikesEnvironmentEnzymesEpidemiologic StudiesEpidemiologyFundingGoalsHandHealthHealth Care CostsHeavy MetalsHumanIncidenceIndividualKnockout MiceLinkMass Spectrum AnalysisMeasuresMedicalMethodsMissense MutationModelingMolecularMotorMotor NeuronsMusMutationNational Health and Nutrition Examination SurveyNerve DegenerationNeurodegenerative DisordersNewly DiagnosedOxidation-ReductionOxidative StressParkinson DiseasePathologyPatientsPharmaceutical PreparationsPopulationPostpoliomyelitis SyndromePreventionPrimary PreventionProcessProteinsQuality of lifeRattusRecyclingReportingResearchRiskRisk FactorsRoleSpinal CordStressSuperoxide DismutaseSupport GroupsSymptomsSyndromeSystemTestingTherapeuticThioctic AcidTissuesTocopherolsTocotrienolsToxic ActionsToxic effectTransgenic AnimalsTransgenic MiceTransgenic OrganismsUbiquinoneUnited States National Institutes of HealthVitamin EWorkZincZinc deficiencyaging brainaging populationanalytical toolantioxidant therapyascorbatebasecopper zinc superoxide dismutasecostdietary antioxidantimprovedinnovationmortalitymouse modelmuscle degenerationmutantnervous system disordernovelnutritionpreventrespiratorytooltranscription factor
项目摘要
The quality of life of ALS patients has substantially improved in the past decade from better nutrition,
respiratory support and a variety of complementary and alternative medicines (CAM). CAM for ALS patients
is well accepted by the traditional medical community. Our long-term goal is to find a combination of
therapeutic actions to slow the progressive death of motor neurons that defines ALS, turning this fatal
disease into a chronic condition resembling post-polio syndrome. An important clue came from discovering
mutations to the antioxidant copper, zinc superoxide dismutase cause 2-3% of ALS patients. We found that
the loss of zinc from SOD, which is favored by the mutations, is toxic to motor neurons by increasing nitrative
stress, suggesting zinc status could link the 2% familial SOD patients with the remaining 98% of ALS
patients. Our research has also shown that nitrative stress in astrocytes surrounding motor neurons
contributes to the progressive death of motor neurons. Expression of ALS-mutant SODs in transgenic mice
and rats is now widely used to study the effects of both traditional as well as CAM therapies on survival. With
a better understanding of how SOD malfunctions to cause ALS, we have identified several novel CAM
antioxidant therapies that could modulate the progression of ALS. Using a combination of cell culture and
microanalytical methods of spinal cord from transgenic rats, we will characterize the ability of CAM therapies
to modulate disease progression in these animals. Our first aim is to determine whether zinc can slow the
progression of ALS in transgenic SOD rats and whether heavy metal chelation therapy unintentionally may
accelerate ALS by removing zinc. Our second aim will characterize whether the depletion of ascorbate by
zinc deficient SOD makes the spinal cord vulnerable to a-tocopherol deficiencies. Our final aim will
characterize whether lipoic acid can ameliorate the effects of a-tocopherol deficiency or reduce the toxic
effects of SOD in aging rats. Our proposed studies will provide a mechanistic basis for examining how CAM
antioxidant therapies can be coordinated to modulate the course of ALS.
过去十年,由于营养改善,ALS 患者的生活质量得到了显着改善,
呼吸支持和各种补充和替代药物 (CAM)。 ALS 患者的 CAM
被传统医学界广泛接受。我们的长期目标是找到一个组合
治疗行动可减缓 ALS 运动神经元的进行性死亡,从而扭转这种致命性
疾病转变为类似于脊髓灰质炎后综合症的慢性疾病。一条重要的线索来自于发现
抗氧化剂铜、锌超氧化物歧化酶突变导致 2-3% 的 ALS 患者。我们发现
SOD 中锌的损失(突变有利于这种情况)通过增加硝化作用而对运动神经元产生毒性
压力,表明锌状态可能将 2% 的家族性 SOD 患者与其余 98% 的 ALS 患者联系起来
患者。我们的研究还表明运动神经元周围星形胶质细胞的硝化应激
导致运动神经元的进行性死亡。 ALS 突变型 SOD 在转基因小鼠中的表达
现在,老鼠被广泛用于研究传统疗法和 CAM 疗法对生存的影响。和
为了更好地了解 SOD 故障如何导致 ALS,我们发现了几种新颖的 CAM
抗氧化疗法可以调节 ALS 的进展。结合使用细胞培养和
转基因大鼠脊髓的微量分析方法,我们将表征 CAM 疗法的能力
调节这些动物的疾病进展。我们的首要目标是确定锌是否可以减缓
转基因 SOD 大鼠 ALS 的进展以及重金属螯合疗法是否无意中可能会导致
通过去除锌来加速 ALS。我们的第二个目标将表征抗坏血酸的消耗是否通过
缺乏锌的 SOD 会使脊髓容易缺乏α-生育酚。我们的最终目标是
表征硫辛酸是否可以改善α-生育酚缺乏的影响或降低毒性
SOD 对衰老大鼠的影响。我们提出的研究将为检验 CAM 如何提供机制基础
可以协调抗氧化疗法来调节 ALS 的病程。
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 }}
JOSEPH S BECKMAN其他文献
JOSEPH S BECKMAN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('JOSEPH S BECKMAN', 18)}}的其他基金
Reducing Susceptibility to Environmental Stress Throughout the Life Span
降低整个生命周期对环境压力的敏感性
- 批准号:
7901764 - 财政年份:2009
- 资助金额:
$ 30.86万 - 项目类别:
Superoxide Dismutase, Peroxynitrite and ALS
超氧化物歧化酶、过氧亚硝酸盐和 ALS
- 批准号:
8269706 - 财政年份:2008
- 资助金额:
$ 30.86万 - 项目类别:
Superoxide Dismutase, Peroxynitrite and ALS
超氧化物歧化酶、过氧亚硝酸盐和 ALS
- 批准号:
7624971 - 财政年份:2008
- 资助金额:
$ 30.86万 - 项目类别:
Superoxide Dismutase, Peroxynitrite and ALS
超氧化物歧化酶、过氧亚硝酸盐和 ALS
- 批准号:
7527886 - 财政年份:2008
- 资助金额:
$ 30.86万 - 项目类别:
Superoxide Dismutase, Peroxynitrite and ALS
超氧化物歧化酶、过氧亚硝酸盐和 ALS
- 批准号:
7848812 - 财政年份:2008
- 资助金额:
$ 30.86万 - 项目类别:
Superoxide Dismutase, Peroxynitrite and ALS
超氧化物歧化酶、过氧亚硝酸盐和 ALS
- 批准号:
8073045 - 财政年份:2008
- 资助金额:
$ 30.86万 - 项目类别:
Functional Significance of Tyrosine Nitration in Proteins
蛋白质中酪氨酸硝化的功能意义
- 批准号:
7559166 - 财政年份:2007
- 资助金额:
$ 30.86万 - 项目类别:
相似海外基金
How novices write code: discovering best practices and how they can be adopted
新手如何编写代码:发现最佳实践以及如何采用它们
- 批准号:
2315783 - 财政年份:2023
- 资助金额:
$ 30.86万 - 项目类别:
Standard Grant
One or Several Mothers: The Adopted Child as Critical and Clinical Subject
一位或多位母亲:收养的孩子作为关键和临床对象
- 批准号:
2719534 - 财政年份:2022
- 资助金额:
$ 30.86万 - 项目类别:
Studentship
A material investigation of the ceramic shards excavated from the Omuro Ninsei kiln site: Production techniques adopted by Nonomura Ninsei.
对大室仁清窑遗址出土的陶瓷碎片进行材质调查:野野村仁清采用的生产技术。
- 批准号:
20K01113 - 财政年份:2020
- 资助金额:
$ 30.86万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2633211 - 财政年份:2020
- 资助金额:
$ 30.86万 - 项目类别:
Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2436895 - 财政年份:2020
- 资助金额:
$ 30.86万 - 项目类别:
Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2633207 - 财政年份:2020
- 资助金额:
$ 30.86万 - 项目类别:
Studentship
A Study on Mutual Funds Adopted for Individual Defined Contribution Pension Plans
个人设定缴存养老金计划采用共同基金的研究
- 批准号:
19K01745 - 财政年份:2019
- 资助金额:
$ 30.86万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The limits of development: State structural policy, comparing systems adopted in two European mountain regions (1945-1989)
发展的限制:国家结构政策,比较欧洲两个山区采用的制度(1945-1989)
- 批准号:
426559561 - 财政年份:2019
- 资助金额:
$ 30.86万 - 项目类别:
Research Grants
Securing a Sense of Safety for Adopted Children in Middle Childhood
确保被收养儿童的中期安全感
- 批准号:
2236701 - 财政年份:2019
- 资助金额:
$ 30.86万 - 项目类别:
Studentship
Structural and functional analyses of a bacterial protein translocation domain that has adopted diverse pathogenic effector functions within host cells
对宿主细胞内采用多种致病效应功能的细菌蛋白易位结构域进行结构和功能分析
- 批准号:
415543446 - 财政年份:2019
- 资助金额:
$ 30.86万 - 项目类别:
Research Fellowships