用 BDNF 刺激髓鞘恢复:治疗阿尔茨海默病的有效方法

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Ioanna Zota, Konstantina Chanoumidou, Achille Gravanis, Ioannis Charalampopoulos
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引用次数: 0

摘要

阿尔茨海默病(AD)是一种慢性神经退行性疾病,是最常见的痴呆症(占 60%-70% 的病例)。虽然阿尔茨海默病主要表现为神经退行性病变,但最近的临床证据表明,髓鞘损伤是疾病发病机制中的一个关键因素。由于缺乏预防性或恢复性治疗方法,因此需要开发针对疾病病因的新型治疗方法。最近在动物和患者身上进行的研究强调,除了淀粉样蛋白斑块和神经纤维缠结的形成之外,神经元轴突髓鞘化的丧失也是导致注意力缺失症病情恶化的一个重要因素,而淀粉样蛋白斑块和神经纤维缠结是迄今为止该疾病的主要病理特征。髓鞘破坏是注意力缺失症的早期症状。然而,目前还不清楚髓鞘脱落是仅仅归因于组织炎症过程等外源性因素,还是也归因于少突生成受损。神经营养因子是神经组织在许多病理条件下公认的保护性分子,也有助于适当的髓鞘化。由于神经营养因子不能作为药物使用,许多研究工作都集中在用小分子替代神经营养因子的活性上。我们的研究团队最近开发出了新型微分子合成神经营养素模拟物(MNTs),可选择性地作用于神经营养素受体,从而为针对神经退行性疾病的创新疗法提供了独特的机会。这些亲脂性小分子不仅能解决这些疾病的潜在生物效应(神经保护作用),还能发挥显著的神经源作用,诱导疾病区域的神经元替代。中枢神经系统中重要的神经营养素分子之一是脑源性神经营养素因子(BDNF)。BDNF 是一种神经营养素,不仅支持神经保护和成人神经发生,还能在中枢神经系统中介导促进髓鞘形成的作用。BDNF 与 TrkB 神经营养素受体具有高亲和力,可通过增加少突胶质祖细胞(OPCs)的密度来增强髓鞘化,在中枢神经系统髓鞘化中发挥重要作用。最后,在本综述中,我们讨论了阿尔茨海默病的髓鞘病理生理学,以及神经营养素,特别是 BDNF 在髓鞘维持和恢复中的作用,揭示了其对阿尔茨海默病的宝贵治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Stimulating myelin restoration with BDNF: a promising therapeutic approach for Alzheimer's disease
Alzheimer's Disease (AD) is a chronic neurodegenerative disorder constituting the most common form of dementia (60%−70% of cases). Although AD presents majorly a neurodegenerative pathology, recent clinical evidence highlights myelin impairment as a key factor in disease pathogenesis. The lack of preventive or restorative treatment is emphasizing the need to develop novel therapeutic approaches targeting to the causes of the disease. Recent studies in animals and patients have highlighted the loss of myelination of the neuronal axons as an extremely aggravating factor in AD, in addition to the formation of amyloid plaques and neurofibrillary tangles that are to date the main pathological hallmarks of the disease. Myelin breakdown represents an early stage event in AD. However, it is still unclear whether myelin loss is attributed only to exogenous factors like inflammatory processes of the tissue or to impaired oligodendrogenesis as well. Neurotrophic factors are well established protective molecules under many pathological conditions of the neural tissue, contributing also to proper myelination. Due to their inability to be used as drugs, many research efforts are focused on substituting neurotrophic activity with small molecules. Our research team has recently developed novel micromolecular synthetic neurotrophin mimetics (MNTs), selectively acting on neurotrophin receptors, and thus offering a unique opportunity for innovative therapies against neurodegenerative diseases. These small sized, lipophilic molecules address the underlying biological effect of these diseases (neuroprotective action), but also they exert significant neurogenic actions inducing neuronal replacement of the disease areas. One of the significant neurotrophin molecules in the Central Nervous System is Brain-Derived-Neurotrophin-Factor (BDNF). BDNF is a neurotrophin that not only supports neuroprotection and adult neurogenesis, but also mediates pro-myelinating effects in the CNS. BDNF binds with high-affinity on the TrkB neurotrophin receptor and enhances myelination by increasing the density of oligodendrocyte progenitor cells (OPCs) and playing an important role in CNS myelination. Conclusively, in the present review, we discuss the myelin pathophysiology in Alzheimer's Diseases, as well as the role of neurotrophins, and specifically BDNF, in myelin maintenance and restoration, revealing its valuable therapeutic potential against AD.
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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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