Basal lamina changes in neurodegenerative disorders.
Basal lamina changes in neurodegenerative disorders.
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DOI：
10.1186/s13024-021-00502-y
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发表时间：
2021-12-07
影响因子：
15.1
通讯作者：
Yao Y
中科院分区：
文献类型：
--
作者：
Nguyen B;Bix G;Yao Y
神经退行性疾病是一组年龄相关性疾病，其特征在于CNS的结构和功能的进行性退化。这些疾病的两个关键病理特征是血脑屏障（BBB）破坏和蛋白质聚集。血脑屏障由多种细胞和一个非细胞成分--基底层（BL）组成。虽然不同的细胞如何影响血脑屏障的研究很好，在血脑屏障的维护和功能的BL的作用仍然在很大程度上是未知的。此外，位于血管周围空间，BL也被推测通过脑膜淋巴/胶质淋巴系统调节蛋白质清除。我们实验室和其他实验室最近的研究表明，BL在生理和病理条件下积极调节BBB的完整性和脑膜淋巴/胶质淋巴功能，这表明它可能在神经退行性疾病的发病机制和/或进展中发挥重要作用。在这篇综述中，我们专注于BL及其主要成分在衰老过程中的变化和神经退行性疾病，包括阿尔茨海默病（AD），帕金森病（PD）和肌萎缩侧索硬化症（ALS）。首先，我们介绍中枢神经系统的血管和淋巴系统。接下来，我们讨论了BL和它的主要组成部分在稳态条件下，并总结了他们的变化在衰老过程中，在AD，PD和ALS在啮齿动物和人类。这些变化的功能意义和潜在的治疗靶点也进行了审查。最后，在该领域的主要挑战和未来的发展方向进行了讨论。了解BL的变化和这些变化在神经退行性疾病中的功能意义将填补该领域知识的差距。我们的目标是提供一个清晰和简洁的审查BL和神经退行性疾病之间的复杂关系，以刺激新的假设和进一步的研究在这一领域。
Neurodegenerative disorders are a group of age-associated diseases characterized by progressive degeneration of the structure and function of the CNS. Two key pathological features of these disorders are blood-brain barrier (BBB) breakdown and protein aggregation. The BBB is composed of various cell types and a non-cellular component---the basal lamina (BL). Although how different cells affect the BBB is well studied, the roles of the BL in BBB maintenance and function remain largely unknown. In addition, located in the perivascular space, the BL is also speculated to regulate protein clearance via the meningeal lymphatic/glymphatic system. Recent studies from our laboratory and others have shown that the BL actively regulates BBB integrity and meningeal lymphatic/glymphatic function in both physiological and pathological conditions, suggesting that it may play an important role in the pathogenesis and/or progression of neurodegenerative disorders. In this review, we focus on changes of the BL and its major components during aging and in neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). First, we introduce the vascular and lymphatic systems in the CNS. Next, we discuss the BL and its major components under homeostatic conditions, and summarize their changes during aging and in AD, PD, and ALS in both rodents and humans. The functional significance of these alterations and potential therapeutic targets are also reviewed. Finally, key challenges in the field and future directions are discussed. Understanding BL changes and the functional significance of these changes in neurodegenerative disorders will fill the gap of knowledge in the field. Our goal is to provide a clear and concise review of the complex relationship between the BL and neurodegenerative disorders to stimulate new hypotheses and further research in this field.
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