HTS to identify compounds that increase NAD+ levels in neurons and muscle cells
HTS 鉴定可增加神经元和肌肉细胞中 NAD 水平的化合物
基本信息
- 批准号:10618481
- 负责人:
- 金额:$ 27.94万
- 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:2022-06-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:ADME StudyAlzheimer&aposs DiseaseBiological AssayBiologyBrain IschemiaCell LineCell physiologyCellsCellular StressCessation of lifeChemicalsCollaborationsCollectionComputer AnalysisConsumptionDNA DamageDementiaDermatitisDevelopmentDiarrheaDiseaseDoseDrug KineticsDuchenne muscular dystrophyEnzymesFDA approvedFunctional disorderGenomicsGrantHereditary DiseaseHomeostasisHumanIn VitroKineticsLibrariesLinkLuciferasesMass Spectrum AnalysisMetabolicMetabolic DiseasesMetabolismMitochondriaMitochondrial MyopathiesMusMuscleMuscle CellsMutationMyopathyNADHNerve DegenerationNeurologicNeuromuscular DiseasesNeuronsNiacinamideNicotinamide adenine dinucleotideNicotinic AcidsOxidation-ReductionOxidesPathway interactionsPatientsPellagraPermeabilityPharmaceutical ChemistryPharmacologyPhasePrPProcessProductionRecyclingReportingResearch PersonnelRhabdomyosarcomaRodentSecondary toSignal TransductionSkeletal MuscleSolubilitySyndromeTestingTherapeuticToxic effectTryptophanUnhealthy DietUp-RegulationValidationage relatedassay developmentaxonal degenerationbasecheminformaticscofactordietaryenzyme pathwayhigh throughput screeningin silicoliver metabolismmdx mousemouse modelnervous system disorderneuromuscularnicotinamide-beta-ribosidenovelresponsesarcopeniascreeningsmall moleculesmall molecule librariessynergism
项目摘要
Project Summary
Nicotinamide adenine dinucleotide (NAD) is a redox cofactor required by enzymes essential to energy
production and numerous other cellular processes. NAD also serves as a co-substrate for several classes
of signaling enzymes, each of which cleaves the molecule to release nicotinamide. Cellular NAD is derived
from dietary tryptophan (de novo synthesis), nicotinic acid (the Preiss-Handler pathway) or recycled from
nicotinamide via the NAD salvage pathway. NAD deficiency can be triggered by a variety of cellular
stresses, including DNA damage, and is thought to contribute to pathophysiology in a number of metabolic,
neurological, and muscular diseases: conversely, increasing NAD+ has been suggested as a promising
therapeutic strategy. Here, researchers will collaborate to develop and utilize a cellular High Throughput
Screening (HTS) assay to discover and validate small molecules that increase intracellular NAD+ levels.
These studies should identify novel small molecules with great therapeutic potential for a myriad of
neurological and muscular including brain ischemia, Wallerian nerve degeneration, misfolded prion
protein toxicity, Alzheimer's disease (AD), mitochondrial myopathy (MM), age related sarcopenia and
Duchenne's muscular dystrophy(DMD).
项目摘要
烟酰胺腺嘌呤二核苷酸(NAD)是能量必需酶所需的氧化还原辅因子
生产和许多其他细胞过程。NAD还充当几种类别的共底物
每一种酶都能切割分子释放烟酰胺。细胞NAD衍生
从饮食中的色氨酸(从头合成),烟酸(Preiss-peptide途径)或从
烟酰胺通过NAD补救途径。多种细胞可以引发NAD缺乏症
压力,包括DNA损伤,并被认为有助于在一些代谢,
神经和肌肉疾病:相反,增加NAD+被认为是一种有希望的治疗方法。
治疗策略在这里,研究人员将合作开发和利用一种细胞高通量
筛选(HTS)试验,以发现和验证增加细胞内NAD+水平的小分子。
这些研究应该确定新的小分子,具有巨大的治疗潜力,为无数的
神经和肌肉,包括脑缺血、沃勒神经变性、错误折叠朊病毒
蛋白质毒性、阿尔茨海默病(AD)、线粒体肌病(MM)、年龄相关的肌肉减少症和
杜氏肌营养不良症(DMD)。
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)
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Joseph A. Baur其他文献
Human genetics identify convergent signals in mitochondrial LACTB-mediated lipid metabolism in cardiovascular-kidney-metabolic syndrome
人类遗传学确定了心血管-肾脏-代谢综合征中线粒体 LACTB 介导的脂质代谢中的趋同信号。
- DOI:
10.1016/j.cmet.2024.10.007 - 发表时间:
2025-01-07 - 期刊:
- 影响因子:30.900
- 作者:
Shen Li;Hongbo Liu;Hailong Hu;Eunji Ha;Praveena Prasad;Brenita C. Jenkins;Ujjalkumar Subhash Das;Sarmistha Mukherjee;Kyosuke Shishikura;Renming Hu;Daniel J. Rader;Liming Pei;Joseph A. Baur;Megan L. Matthews;Garret A. FitzGerald;Melanie R. McReynolds;Katalin Susztak - 通讯作者:
Katalin Susztak
Mitochondrial NAD+ transporter SLC25A51 linked to human aortic disease
线粒体 NAD+转运蛋白 SLC25A51 与人类主动脉疾病相关
- DOI:
10.1038/s44161-024-00599-6 - 发表时间:
2025-01-22 - 期刊:
- 影响因子:10.800
- 作者:
Gabriel K. Adzika;Ricardo A. Velázquez Aponte;Joseph A. Baur - 通讯作者:
Joseph A. Baur
Swine Models for NAD + Supplementation in Heart Failure
补充 NAD 治疗心力衰竭的猪模型
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Joseph A. Baur - 通讯作者:
Joseph A. Baur
Resveratrol for primary prevention of atherosclerosis: Clinical trial evidence for improved gene expression in vascular endothelium
- DOI:
10.1016/j.ijcard.2012.09.027 - 发表时间:
2013-06-05 - 期刊:
- 影响因子:
- 作者:
Beamon Agarwal;Matthew J. Campen;Meghan M. Channell;Sarah J. Wherry;Behzad Varamini;James G. Davis;Joseph A. Baur;James M. Smoliga - 通讯作者:
James M. Smoliga
Regulation of and challenges in targeting NAD+ metabolism
靶向 NAD+代谢的调控与挑战
- DOI:
10.1038/s41580-024-00752-w - 发表时间:
2024-07-18 - 期刊:
- 影响因子:90.200
- 作者:
Marie E. Migaud;Mathias Ziegler;Joseph A. Baur - 通讯作者:
Joseph A. Baur
Joseph A. Baur的其他文献
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{{ truncateString('Joseph A. Baur', 18)}}的其他基金
Mechanisms and therapeutic potential of blocking the mitochondrial Mg2+ channel Mrs2 in obesity and NAFLD
阻断线粒体 Mg2 通道 Mrs2 在肥胖和 NAFLD 中的机制和治疗潜力
- 批准号:
10679847 - 财政年份:2023
- 资助金额:
$ 27.94万 - 项目类别:
HTS to identify compounds that increase NAD+ levels in neurons and muscle cells
HTS 鉴定可增加神经元和肌肉细胞中 NAD 水平的化合物
- 批准号:
10665088 - 财政年份:2022
- 资助金额:
$ 27.94万 - 项目类别:
Understanding the roles of cardiac NAD pools and therapeutic effects of precursor supplements in heart failure
了解心脏 NAD 池的作用以及前体补充剂对心力衰竭的治疗作用
- 批准号:
10539858 - 财政年份:2022
- 资助金额:
$ 27.94万 - 项目类别:
Understanding the roles of cardiac NAD pools and therapeutic effects of precursor supplements in heart failure
了解心脏 NAD 池的作用以及前体补充剂对心力衰竭的治疗作用
- 批准号:
10680576 - 财政年份:2022
- 资助金额:
$ 27.94万 - 项目类别:
Mechanisms underlying the genetic association between PPP1R3B and Alzheimer's Disease
PPP1R3B 与阿尔茨海默病之间遗传关联的潜在机制
- 批准号:
10288770 - 财政年份:2018
- 资助金额:
$ 27.94万 - 项目类别:
Molecular mechanisms underlying the genetic association between PPP1R3B and hepatic steatosis
PPP1R3B与肝脂肪变性遗传关联的分子机制
- 批准号:
10224175 - 财政年份:2018
- 资助金额:
$ 27.94万 - 项目类别:
Targeting NAD Metabolism to Improve Glucose Homeostasis in Obesity and Aging
靶向 NAD 代谢以改善肥胖和衰老过程中的血糖稳态
- 批准号:
10288703 - 财政年份:2013
- 资助金额:
$ 27.94万 - 项目类别:
Targeting NAD Metabolism to Improve Glucose Homeostasis in Obesity and Aging
靶向 NAD 代谢以改善肥胖和衰老过程中的血糖稳态
- 批准号:
8596305 - 财政年份:2013
- 资助金额:
$ 27.94万 - 项目类别:
Targeting NAD Metabolism to Improve Glucose Homeostasis in Obesity and Aging
靶向 NAD 代谢以改善肥胖和衰老过程中的血糖稳态
- 批准号:
8731882 - 财政年份:2013
- 资助金额:
$ 27.94万 - 项目类别:
Molecular Mechanisms of Rapamycin's effects on Health and longevity.
雷帕霉素对健康和长寿影响的分子机制。
- 批准号:
8852520 - 财政年份:2013
- 资助金额:
$ 27.94万 - 项目类别: