The glymphatic system and Amyotrophic lateral sclerosis
The glymphatic system and Amyotrophic lateral sclerosis
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DOI：
10.1016/j.pneurobio.2024.102571
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发表时间：
2024-01-25
影响因子：
6.7
通讯作者：
Kiernan，Matthew C.
中科院分区：
文献类型：
--
作者：
Eisen，Andrew;Nedergaard，Maiken;Kiernan，Matthew C.
类淋巴系统和脑膜淋巴管提供了运输溶质和清除大脑中有毒物质的途径。与 ALS 特别相关的是，这适用于 TDP-43 和谷氨酸，这两种疾病发病机制的主要元素。血流由动脉搏动、呼吸、姿势以及水通道蛋白 4 通道 (AQP4) 的位置和比例推动。非快速眼动慢波睡眠是类淋巴引流的关键，在清醒时会停止。众所周知，在帕金森病和阿尔茨海默病中，睡眠障碍比典型临床特征的出现要早几年，并且与有毒蛋白质产物的逐渐积累有关。虽然 ALS 中的睡眠问题得到了很好的描述，但很少考虑 ALS 中临床前睡眠障碍或类淋巴系统功能障碍的可能性。在这里，我们回顾一下类淋巴系统如何影响 ALS。临床前睡眠障碍被认为是 ALS 的一个未被认识的主要危险因素，同时探索了改善类淋巴流量的潜在治疗方案。
The glymphatic system and the meningeal lymphatic vessels provide a pathway for transport of solutes and clearance of toxic material from the brain. Of specific relevance to ALS, this is applicable for TDP-43 and glutamate, both major elements in disease pathogenesis. Flow is propelled by arterial pulsation, respiration, posture, as well as the positioning and proportion of aquaporin-4 channels (AQP4). Non-REM slow wave sleep is the is key to glymphatic drainage which discontinues during wakefulness. In Parkinson’s disease and Alzheimer’s disease, sleep impairment is known to predate the development of characteristic clinical features by several years and is associated with progressive accumulation of toxic proteinaceous products. While sleep issues are well described in ALS, consideration of preclinical sleep impairment or the potential of a failing glymphatic system in ALS has rarely been considered. Here we review how the glymphatic system may impact ALS. Preclinical sleep impairment as an unrecognized major risk factor for ALS is considered, while potential therapeutic options to improve glymphatic flow are explored.