CAM Antioxidants and ALS
CAM Antioxidants and ALS
批准号:
7902742
负责人:
JOSEPH S BECKMAN
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
项目状态:
已结题
起止时间:
2009-06-01 至 2013-05-31
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
中文摘要
肌萎缩侧索硬化症患者的生活质量在过去十年中有了很大的改善,
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Administrative CORE
-
批准号:8057621
-
项目类别:
-
资助金额:$41.25万
-
财政年份:2010
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Reducing Susceptibility to Environmental Stress Throughout the Life Span
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批准号:7901764
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项目类别:
-
资助金额:$71.49万
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财政年份:2009
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负责人:JOSEPH S BECKMAN
-
依托单位:
Superoxide Dismutase, Peroxynitrite and ALS
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批准号:8269706
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项目类别:
-
资助金额:$31.34万
-
财政年份:2008
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Superoxide Dismutase, Peroxynitrite and ALS
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批准号:7624971
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项目类别:
-
资助金额:$31.98万
-
财政年份:2008
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Superoxide Dismutase, Peroxynitrite and ALS
-
批准号:7527886
-
项目类别:
-
资助金额:$31.98万
-
财政年份:2008
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Superoxide Dismutase, Peroxynitrite and ALS
-
批准号:7848812
-
项目类别:
-
资助金额:$31.66万
-
财政年份:2008
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Superoxide Dismutase, Peroxynitrite and ALS
-
批准号:8073045
-
项目类别:
-
资助金额:$31.34万
-
财政年份:2008
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Pilot Project Program
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批准号:7240055
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项目类别:
-
资助金额:$36.55万
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财政年份:2007
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Functional Significance of Tyrosine Nitration in Proteins
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批准号:7559166
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项目类别:
-
资助金额:$24.32万
-
财政年份:2007
-
负责人:JOSEPH S BECKMAN
-
依托单位:
CORE--Community Outreach and Education
-
批准号:7458218
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项目类别:
-
资助金额:$14.62万
-
财政年份:2007
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Administrative Core
-
批准号:7240050
-
项目类别:
-
资助金额:$29.24万
-
财政年份:2007
-
负责人:JOSEPH S BECKMAN
-
依托单位:
Astrocytes and motor neuron apoptosis
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批准号:6785990
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项目类别:
-
资助金额:$4.03万
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财政年份:2004
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负责人:JOSEPH S BECKMAN
-
依托单位:
Astrocytes and motor neuron apoptosis
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批准号:6928535
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项目类别:
-
资助金额:$4.03万
-
财政年份:2004
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负责人:JOSEPH S BECKMAN
-
依托单位:
Astrocytes and motor neuron apoptosis
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批准号:6690153
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项目类别:
-
资助金额:$4.03万
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财政年份:2003
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负责人:JOSEPH S BECKMAN
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依托单位:
Third Int'l Conference on Reactive Nitrogen Species
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批准号:6364255
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项目类别:
-
资助金额:$1.6万
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财政年份:2001
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负责人:JOSEPH S BECKMAN
-
依托单位:
Gordon Research Conf--Nitric Oxide in Biochem & Biology
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批准号:6322661
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项目类别:
-
资助金额:$1.5万
-
财政年份:2001
-
负责人:JOSEPH S BECKMAN
-
依托单位:
PEROXYNITRITE AND SOD IN MOTOR NEURON APOPTOSIS
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批准号:6155267
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项目类别:
-
资助金额:$4.4万
-
财政年份:1998
-
负责人:JOSEPH S BECKMAN
-
依托单位:
PEROXYNITRITE AND SOD IN MOTOR NEURON APOPTOSIS
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批准号:2892317
-
项目类别:
-
资助金额:$22.27万
-
财政年份:1998
-
负责人:JOSEPH S BECKMAN
-
依托单位:
PEROXYNITRITE AND NITROTYROSINE IN HEART DISEASE
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批准号:2857933
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项目类别:
-
资助金额:$29.73万
-
财政年份:1998
-
负责人:JOSEPH S BECKMAN
-
依托单位:
PEROXYNITRITE AND NITROTYROSINE IN HEART DISEASE
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批准号:2465772
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项目类别:
-
资助金额:$30.8万
-
财政年份:1998
-
负责人:JOSEPH S BECKMAN
-
依托单位:
海外基金