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中文摘要
翻译
病理上,多发性硬化症(MS)可以通过弥漫性、离散性的存在来识别 脱髓鞘区域,称为斑块。脱髓鞘是多发性硬化症的主要特征,因此, 多发性硬化症的治疗方法包括增加轴突的重新髓鞘形成,导致 临床改善。过氧化物酶体增殖物激活受体β或δ(PPARβ)高表达 在中枢神经系统中表达,参与许多脑功能,包括髓鞘形成。成为一名 核激素受体PPARβ的激活和核转位需要配体S的参与。 因此,寻找新的无毒的PPARβ配基具有重要的意义。 促进髓鞘再生。β-羟基β-甲基丁酸酯(HMB)在当地GNC中可用 作为人体肌肉建设的补充剂。它是一种生理分子,它是由 在人体内通过代谢L-亮氨酸。众所周知,HMB可以增加运动诱导的 增加肌肉大小和肌肉力量,提高运动成绩。我们的预赛 结果表明,HMB可结合和激活PPARβ,并促进其成熟。 少突胶质前体细胞(OPC)向少突胶质细胞(OL)转化,髓鞘生成细胞 中枢神经系统。因此,在这里,我们将检验一个令人兴奋的假设,即HMB与配体结合- PPARβ与HMB及其前体L亮氨酸结合结构域促进胚胎成熟 OPC和刺激动物模型中的再髓鞘形成(铜和实验性变态反应 脑脊髓炎)的中枢神经系统脱髓鞘通过PPARβ。 行政补充:阿尔茨海默病(AD)是最常见的神经退行性疾病 尽管进行了密集的研究,但还没有有效的治疗方法来阻止这种 AD的进展。有趣的是,我们的初步结果显示 死后阿尔茨海默病患者脑的海马区和皮质区与年龄匹配的对照组比较 没有认知障碍。同样,我们已经在海马体中看到脱髓鞘和 5XFAD小鼠的大脑皮质,但不是年龄匹配的非转基因小鼠。因为肌肉的生长 补充HMB激活PPARβ,增加髓鞘特异基因并刺激 OPC对OL的成熟,在这里,回应NOT-AG-20-034,题为“特别通知” 兴趣:针对阿尔茨海默氏症的NIH补助金的行政补充没有重点关注 阿尔茨海默病“,我们计划测试一个令人兴奋的假设,口服给药 HMB及其前体Leu刺激再髓鞘形成并改善认知功能 5PPARβ诱导的AD小鼠模型。这一行政副刊的积极成果 将表明脱髓鞘/重新髓鞘是否为AD的治疗靶点,增强 阿尔茨海默病患者促进髓鞘再生和改善认知功能的可能性 肌肉增强剂HMB和一种简单的无毒氨基酸L-亮氨酸为主要或 辅助治疗。
英文摘要
Pathologically, multiple sclerosis (MS) can be identified by the presence of diffuse, discrete demyelinated areas, called plaques. Demyelination is a major feature of MS and therefore, an approach to the management of MS involves an increase in remyelination of axons, resulting in clinical improvement. Peroxisome proliferator-activated receptor β or δ (PPARβ) being highly expressed in the CNS participates in many brain functions including myelination. Being a nuclear hormone receptor, PPARβ needs ligand(s) for its activation and nuclear translocation. Therefore, identification of new nontoxic ligand of PPARβ would be very important for promoting remyelination. The β-hydroxy β-methylbutyrate (HMB) is available in local GNC stores as a muscle-building supplement in human. It is a physiological molecule that is produced in human through the metabolism of L-leucine. HMB is known to increase exercise-induced gains in muscle size and muscle strength and improve exercise performance. Our preliminary results show that HMB may bind and activate PPARβ and stimulate the maturation of oligodendroglial progenitor cells (OPCs) to oligodendrocytes (OL), myelin-producing cells in the CNS. Therefore, here, we will test an exciting hypothesis that HMB binds to the ligand- binding domain of PPARβ and that HMB and its precursor L-leucine promote maturation of OPCs and stimulate remyelination in animal models (cuprizone and experimental allergic encephalomyelitis) of CNS demyelination via PPARβ. Administrative supplement: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in humans and despite intense investigations, no effective therapy is available to halt the progression of AD. Interestingly, our preliminary results show marked demyelination in the hippocampus and cortex of postmortem AD brains as compared to age-matched control brains with no cognitive impairment. Similarly, we have seen demyelination in the hippocampus and cortex of 5XFAD mice, but not age-matched non-transgenic mice. Since the muscle building supplement HMB activates PPARβ, increases myelin-specific genes and stimulates the maturation of OPC to OL, here, in response to NOT-AG-20-034 entitled “Notice of Special Interest: Alzheimer’s-focused administrative supplements for NIH grants that are not focused on Alzheimer’s disease”, we have planned to test an exciting hypothesis that oral administration of HMB and its precursor Leu stimulates remyelination and improves cognitive functions in 5XFAD mouse model of AD via PPARβ. A positive outcome of this administrative supplement will indicate whether demyelination/remyelination is a therapeutic target in AD, enhance the possibility of promoting remyelination and improving cognitive functions in AD patients with muscle-building supplement HMB and a simple non-toxic amino acid L-leucine as primary or adjunct therapy.
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Remyelination by intranasal TIDM peptide
  • 批准号:
    10582863
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2023
  • 负责人:
    KALIPADA PAHAN
  • 依托单位:
Intranasal TIDM peptide for tauopathy
  • 批准号:
    10274908
  • 项目类别:
  • 资助金额:
    $15.7万
  • 财政年份:
    2020
  • 负责人:
    KALIPADA PAHAN
  • 依托单位:
Muscle building supplement HMB for remyelination
  • 批准号:
    10442389
  • 项目类别:
  • 资助金额:
    $39.25万
  • 财政年份:
    2020
  • 负责人:
    KALIPADA PAHAN
  • 依托单位:
Cinnamon and traumatic brain injury
  • 批准号:
    10553165
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2020
  • 负责人:
    KALIPADA PAHAN
  • 依托单位:
国内基金
海外基金
补阳还五汤通过AGE-RAGE通路调控脓毒症免疫失衡的机制与转化研究
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2025
  • 负责人:
  • 依托单位:
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2025
  • 负责人:
    雷芬芳
  • 依托单位:
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    --
  • 批准年份:
    2024
  • 负责人:
    万荣
  • 依托单位: