阿尔茨海默病的星形细胞反应性:促进修复的治疗机会。

IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Current Alzheimer research Pub Date : 2022-01-01 DOI:10.2174/1567205018666211029164106
Nazanin Mirzaei, Nicola Davis, Tsz Wing Chau, Magdalena Sastre
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引用次数: 3

摘要

星形胶质细胞在神经退行性疾病,特别是阿尔茨海默病(AD)中的重要性正在迅速攀升,在淀粉样蛋白-β斑块周围明显存在反应性星形胶质细胞,以及活化的小胶质细胞。反应性星形胶质增生,意味着星形胶质细胞的形态和分子转变,似乎先于神经变性,提示在疾病的发展中起作用。单细胞转录组学最近证明,AD大脑的星形胶质细胞与“正常”健康的星形胶质细胞不同,在神经递质循环(包括谷氨酸和GABA)等领域表现出失调,以及体内平衡功能受损。然而,最近的数据表明,在淀粉样变小鼠模型中,星形胶质细胞的消融导致淀粉样蛋白病理增加,炎症谱恶化,突触密度降低,表明星形胶质细胞介导神经保护作用。因此,针对星形胶质细胞的干预措施可能对阿尔茨海默病有很大的潜力,这一观点得到了一系列药物和干细胞移植研究的支持,这些研究已成功地在阿尔茨海默病小鼠模型中显示出治疗效果。在本文中,我们回顾了关于星形胶质细胞在AD大脑中的作用和概况的最新报道,以及在动物模型中如何操纵星形胶质细胞为使用增强星形胶质细胞功能的治疗方法作为AD的未来治疗途径铺平了道路。
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Astrocyte Reactivity in Alzheimer's Disease: Therapeutic Opportunities to Promote Repair.

Astrocytes are fast climbing the ladder of importance in neurodegenerative disorders, particularly in Alzheimer's Disease (AD), with the prominent presence of reactive astrocytes surrounding amyloid-β plaques, together with activated microglia. Reactive astrogliosis, implying morphological and molecular transformations in astrocytes, seems to precede neurodegeneration, suggesting a role in the development of the disease. Single-cell transcriptomics has recently demonstrated that astrocytes from AD brains are different from "normal" healthy astrocytes, showing dysregulations in areas such as neurotransmitter recycling, including glutamate and GABA, and impaired homeostatic functions. However, recent data suggest that the ablation of astrocytes in mouse models of amyloidosis results in an increase in amyloid pathology, worsening of the inflammatory profile, and reduced synaptic density, indicating that astrocytes mediate neuroprotective effects. The idea that interventions targeting astrocytes may have great potential for AD has therefore emerged, supported by a range of drugs and stem cell transplantation studies that have successfully shown a therapeutic effect in mouse models of AD. In this article, we review the latest reports on the role and profile of astrocytes in AD brains and how manipulation of astrocytes in animal models has paved the way for the use of treatments enhancing astrocytic function as future therapeutic avenues for AD.

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来源期刊
Current Alzheimer research
Current Alzheimer research 医学-神经科学
CiteScore
4.00
自引率
4.80%
发文量
64
审稿时长
4-8 weeks
期刊介绍: Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
期刊最新文献
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