Lei Xia, Yiqiong Qiu, Junjie Li, Mingliang Xu, Zhifang Dong
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They inhibit neuroinflammatory responses by regulating phosphorylation of signal transduction proteins, such as AKT, PI3K, ERK, NF-κB, p38 MAPK, IκBα. In addition, ARTs regulate GABAergic signaling in a dose-dependent manner. Although they competitively inhibit the binding of gephyrin to GABAergic receptors, low doses of ARTs enhance GABAergic signaling. ARTs can also inhibit ferroptosis, activate the Akt/Bcl-2, AMPK, or ERK/CREB pathways to reduce oxidative stress, and maintain mitochondrial homeostasis, protecting neurons from oxidative stress injury. More importantly, ARTs structurally combine with and suppress β-Amyloid (A[Formula: see text]-induced neurotoxicity, reduce P-tau, and maintain O-GlcNAcylation/Phosphorylation balance, leading to relieved pathological changes in neurodegenerative diseases. Collectively, these natural properties endow ARTs with unique potential for application in neurodegenerative diseases.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1641-1660"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Potential Role of Artemisinins Against Neurodegenerative Diseases.\",\"authors\":\"Lei Xia, Yiqiong Qiu, Junjie Li, Mingliang Xu, Zhifang Dong\",\"doi\":\"10.1142/S0192415X24500642\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Artemisinin (ART) and its derivatives, collectively referred to as artemisinins (ARTs), have been approved for the treatment of malaria for decades. ARTs are converted into dihydroartemisinin (DHA), the only active form, which is reductive <i>in vivo</i>. In this review, we provide a brief overview of the neuroprotective potential of ARTs and the underlying mechanisms on several of the most common neurodegenerative diseases, particularly considering their potential application in those associated with cognitive and motor impairments including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). ARTs act as autophagy balancers to alleviate AD and PD. They inhibit neuroinflammatory responses by regulating phosphorylation of signal transduction proteins, such as AKT, PI3K, ERK, NF-κB, p38 MAPK, IκBα. In addition, ARTs regulate GABAergic signaling in a dose-dependent manner. Although they competitively inhibit the binding of gephyrin to GABAergic receptors, low doses of ARTs enhance GABAergic signaling. ARTs can also inhibit ferroptosis, activate the Akt/Bcl-2, AMPK, or ERK/CREB pathways to reduce oxidative stress, and maintain mitochondrial homeostasis, protecting neurons from oxidative stress injury. More importantly, ARTs structurally combine with and suppress β-Amyloid (A[Formula: see text]-induced neurotoxicity, reduce P-tau, and maintain O-GlcNAcylation/Phosphorylation balance, leading to relieved pathological changes in neurodegenerative diseases. 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引用次数: 0
摘要
青蒿素(ART)及其衍生物统称为青蒿素类(ARTs),几十年来一直被批准用于治疗疟疾。青蒿素可转化为双氢青蒿素(DHA),这是唯一的活性形式,在体内具有还原性。在这篇综述中,我们将简要概述 ARTs 的神经保护潜力及其对几种最常见的神经退行性疾病的潜在作用机制,尤其是考虑其在与认知和运动障碍有关的疾病中的潜在应用,包括阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿氏病(HD)和肌萎缩性脊髓侧索硬化症(ALS)。ARTs 可作为自噬平衡剂缓解 AD 和 PD。它们通过调节 AKT、PI3K、ERK、NF-[式中:见正文]B、p38 MAPK、I[式中:见正文]B[式中:见正文]等信号转导蛋白的磷酸化来抑制神经炎症反应。此外,ARTs 还能以剂量依赖性方式调节 GABA 能信号传导。虽然 ARTs 可竞争性地抑制 gephyrin 与 GABA 能受体的结合,但低剂量 ARTs 可增强 GABA 能信号传导。ARTs 还能抑制铁凋亡,激活 Akt/Bcl-2、AMPK 或 ERK/CREB 通路以减少氧化应激,维持线粒体平衡,保护神经元免受氧化应激损伤。更重要的是,ARTs 从结构上结合并抑制淀粉样蛋白(A[式:见正文])诱导的神经毒性,降低 P-tau,维持 O-GlcNAcylation/Phosphorylation 平衡,从而缓解神经退行性疾病的病理变化。这些天然特性共同赋予了 ARTs 在神经退行性疾病中应用的独特潜力。
The Potential Role of Artemisinins Against Neurodegenerative Diseases.
Artemisinin (ART) and its derivatives, collectively referred to as artemisinins (ARTs), have been approved for the treatment of malaria for decades. ARTs are converted into dihydroartemisinin (DHA), the only active form, which is reductive in vivo. In this review, we provide a brief overview of the neuroprotective potential of ARTs and the underlying mechanisms on several of the most common neurodegenerative diseases, particularly considering their potential application in those associated with cognitive and motor impairments including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). ARTs act as autophagy balancers to alleviate AD and PD. They inhibit neuroinflammatory responses by regulating phosphorylation of signal transduction proteins, such as AKT, PI3K, ERK, NF-κB, p38 MAPK, IκBα. In addition, ARTs regulate GABAergic signaling in a dose-dependent manner. Although they competitively inhibit the binding of gephyrin to GABAergic receptors, low doses of ARTs enhance GABAergic signaling. ARTs can also inhibit ferroptosis, activate the Akt/Bcl-2, AMPK, or ERK/CREB pathways to reduce oxidative stress, and maintain mitochondrial homeostasis, protecting neurons from oxidative stress injury. More importantly, ARTs structurally combine with and suppress β-Amyloid (A[Formula: see text]-induced neurotoxicity, reduce P-tau, and maintain O-GlcNAcylation/Phosphorylation balance, leading to relieved pathological changes in neurodegenerative diseases. Collectively, these natural properties endow ARTs with unique potential for application in neurodegenerative diseases.