Alexander's Disease: Potential Drug Targets and Future Directions.

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Molecular Neurobiology Pub Date : 2025-11-01 Epub Date: 2025-05-31 DOI:10.1007/s12035-025-05083-1
Emily Zavala, Tahl Zimmerman
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引用次数: 0

Abstract

Alexander's disease is a rare neurodegenerative disorder primarily characterized by upregulation of the GFAP gene and the formation of Rosenthal fibers. Its prognosis is fatal, with limited treatment options currently available. The GFAP protein is a marker for mature astrocytes. It results in the upregulation of reactive astroglioses. Reactive astroglioses is a neuroprotective condition that, when functioning correctly, helps protect the brain from stress and injury and prevents further injury. However, unregulated reactive astroglioses is linked with many neurodegenerative diseases. Due to the relative rarity in the incidence of AxD, treatment options have not been as widely investigated. This review explores potential drug targets that may impact GFAP gene expression, such as STAT3, GDNF, NF-kB, LCN-2, and the LPS pathway. These drug targets have previously been or are currently being explored in other neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. The only treatment option currently in clinical trial phases involves methods to induce the knockout of the GFAP gene. Due to GFAP's neuroprotective role in brain injury and stress, it is important to explore alternative treatment options that downregulate GFAP as opposed to shutting it off entirely.

亚历山大病:潜在的药物靶点和未来方向。
亚历山大氏病是一种罕见的神经退行性疾病,主要特征是GFAP基因上调和罗森塔尔纤维的形成。其预后是致命的,目前可用的治疗方案有限。GFAP蛋白是成熟星形胶质细胞的标志。它导致反应性星形胶质细胞的上调。反应性星形胶质是一种神经保护疾病,当功能正常时,有助于保护大脑免受压力和伤害,并防止进一步的伤害。然而,不受管制的反应性星形胶质与许多神经退行性疾病有关。由于AxD的发病率相对较低,治疗方案尚未得到广泛研究。本综述探讨了可能影响GFAP基因表达的潜在药物靶点,如STAT3、GDNF、NF-kB、LCN-2和LPS通路。这些药物靶点以前已经或正在探索其他神经退行性疾病,如帕金森病和阿尔茨海默病。目前处于临床试验阶段的唯一治疗选择涉及诱导GFAP基因敲除的方法。由于GFAP在脑损伤和应激中的神经保护作用,探索下调GFAP的替代治疗方案而不是完全关闭它是很重要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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