期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 14, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2021.647895
关键词
amyotrophic lateral sclerosis; cerebrospinal fluid; motor neuron disease; neurodegeneration; pathophysiology; toxicity
资金
- Medical Research Council (MRC)
- Motor Neurone Disease Association [MR/R001162/1]
- Rowling Scholars scheme
- Chief Scientist Office
- RS Macdonald Charitable Trust via the Scottish Neurological Research Fund
- Euan MacDonald Centre for Motor Neurone Disease Research
- UK Dementia Research Institute (DRI)
- MRC
- Alzheimer's Society
- Alzheimer's Research UK
- UK DRI Ltd.
- MRC [UKDRI-4003, UKDRI-4001, MR/R001162/1] Funding Source: UKRI
This review summarizes the 40-year history of CSF toxicity studies in ALS and discusses various proposed mechanisms such as glutamate excitotoxicity, proteotoxicity, and oxidative stress. The potential implications of a toxic CSF circulatory system in the pathophysiology of ALS and its significance in current ALS research are also considered.
Based on early evidence of in vitro neurotoxicity following exposure to serum derived from patients with amyotrophic lateral sclerosis (ALS), several studies have attempted to explore whether cerebrospinal fluid (CSF) obtained from people with ALS could possess similar properties. Although initial findings proved inconclusive, it is now increasingly recognized that ALS-CSF may exert toxicity both in vitro and in vivo. Nevertheless, the mechanism underlying CSF-induced neurodegeneration remains unclear. This review aims to summarize the 40-year long history of CSF toxicity studies in ALS, while discussing the various mechanisms that have been proposed, including glutamate excitotoxicity, proteotoxicity and oxidative stress. Furthermore, we consider the potential implications of a toxic CSF circulatory system in the pathophysiology of ALS, and also assess its significance in the context of current ALS research.
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