肌萎缩性脊髓侧索硬化症(ALS)的新靶点:ATP结合盒(ABC)转运体调节的前景。

IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Behavioural Brain Research Pub Date : 2024-09-05 DOI:10.1016/j.bbr.2024.115242
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引用次数: 0

摘要

肌萎缩性脊髓侧索硬化症(ALS)是一种进行性神经退行性疾病,主要影响运动神经元,导致残疾和神经元死亡,而ATP结合小卡(ABC)转运体因其在药物外流和调控各种细胞通路中的作用而有助于ALS的发病。在本文中,我们广泛研究了 ALS 转运体与 ALS 发病机制相关的各种分子和机制途径;这涉及炎症通路,如丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3-激酶/蛋白激酶 B(PI3K/Akt)、Toll-Like 受体(TLR)、糖原合成酶激酶 3β (GSK-3β)、核因子卡巴-B(NF-κB)和环氧化酶(COX)。氧化途径,如星形胶质细胞、谷氨酸、类核因子(红细胞衍生 2)2(Nrf2)、Sirtuin 1(SIRT-1)、叉头盒蛋白 O(FOXO)、细胞外信号调节激酶(ERK)。此外,我们还深入研究了自噬途径的作用,如 TAR DNA 结合蛋白 43 (TDP-43)、AMP 激活蛋白激酶 (AMPK)、哺乳动物雷帕霉素靶标 (mTOR),最后是凋亡途径。此外,通过了解这些错综复杂的相互作用,我们希望开发出针对 ABC 转运体的新型治疗策略,改善药物输送,最终为治疗渐冻人症提供一条前景广阔的途径。
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Emerging targets in amyotrophic lateral sclerosis (ALS): The promise of ATP-binding cassette (ABC) transporter modulation

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative primarily affecting motor neurons, leading to disability and neuronal death, and ATP-Binding Cassette (ABC) transporter due to their role in drug efflux and modulation of various cellular pathways contributes to the pathogenesis of ALS. In this article, we extensively investigated various molecular and mechanistic pathways linking ALS transporter to the pathogenesis of ALS; this involves inflammatory pathways such as Mitogen-Activated Protein Kinase (MAPK), Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/Akt), Toll-Like Receptor (TLR), Glycogen Synthase Kinase 3β (GSK-3β), Nuclear Factor Kappa-B (NF-κB), and Cyclooxygenase (COX). Oxidative pathways such as Astrocytes, Glutamate, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin 1 (SIRT-1), Forkhead box protein O (FOXO), Extracellular signal-regulated kinase (ERK). Additionally, we delve into the role of autophagic pathways like TAR DNA-binding protein 43 (TDP-43), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and lastly, the apoptotic pathways. Furthermore, by understanding these intricate interactions, we aim to develop novel therapeutic strategies targeting ABC transporters, improving drug delivery, and ultimately offering a promising avenue for treating ALS.

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来源期刊
Behavioural Brain Research
Behavioural Brain Research 医学-行为科学
CiteScore
5.60
自引率
0.00%
发文量
383
审稿时长
61 days
期刊介绍: Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.
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