AUTHOR=Ng Kee Kwong Koy Chong , Harbham Pratap K. , Selvaraj Bhuvaneish T. , Gregory Jenna M. , Pal Suvankar , Hardingham Giles E. , Chandran Siddharthan , Mehta Arpan R. 

TITLE=40 Years of CSF Toxicity Studies in ALS: What Have We Learnt About ALS Pathophysiology?

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=14

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.647895

DOI=10.3389/fnmol.2021.647895

ISSN=1662-5099

ABSTRACT=<p>Based on early evidence of <italic>in vitro</italic> 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 <italic>in vitro</italic> and <italic>in vivo</italic>. 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.</p>