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.

中文翻译：

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神经退行性疾病中基底层的变化

神经退行性疾病是一组与年龄相关的疾病，其特征是中枢神经系统结构和功能进行性退化。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。BBB 由多种细胞类型和非细胞成分——基底层（BL）组成。尽管不同细胞如何影响 BBB 已得到充分研究，但 BL 在 BBB 维持和功能中的作用仍然很大程度上未知。此外，BL 位于血管周围空间，也被推测通过脑膜淋巴/类淋巴系统调节蛋白质清除。我们实验室和其他实验室的最新研究表明，BL 在生理和病理条件下积极调节 BBB 完整性和脑膜淋巴/类淋巴功能，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，我们重点关注衰老过程中和神经退行性疾病（包括阿尔茨海默病 (AD)、帕金森病 (PD) 和肌萎缩侧索硬化症 (ALS)）中 BL 及其主要成分的变化。首先，我们介绍中枢神经系统的血管和淋巴系统。接下来，我们讨论稳态条件下的 BL 及其主要成分，并总结它们在啮齿动物和人类的衰老过程中以及 AD、PD 和 ALS 中的变化。还回顾了这些改变的功能意义和潜在的治疗靶点。最后，讨论了该领域的主要挑战和未来的方向。了解 BL 变化以及这些变化在神经退行性疾病中的功能意义将填补该领域的知识空白。我们的目标是对 BL 和神经退行性疾病之间的复杂关系进行清晰、简洁的回顾，以激发该领域的新假设和进一步研究。