Frontiers in Molecular Neuroscience (Mar 2021)
40 Years of CSF Toxicity Studies in ALS: What Have We Learnt About ALS Pathophysiology?
- Koy Chong Ng Kee Kwong,
- Pratap K. Harbham,
- Bhuvaneish T. Selvaraj,
- Bhuvaneish T. Selvaraj,
- Bhuvaneish T. Selvaraj,
- Jenna M. Gregory,
- Jenna M. Gregory,
- Jenna M. Gregory,
- Jenna M. Gregory,
- Jenna M. Gregory,
- Suvankar Pal,
- Suvankar Pal,
- Suvankar Pal,
- Giles E. Hardingham,
- Giles E. Hardingham,
- Giles E. Hardingham,
- Siddharthan Chandran,
- Siddharthan Chandran,
- Siddharthan Chandran,
- Siddharthan Chandran,
- Siddharthan Chandran,
- Arpan R. Mehta,
- Arpan R. Mehta,
- Arpan R. Mehta,
- Arpan R. Mehta,
- Arpan R. Mehta
Affiliations
- Koy Chong Ng Kee Kwong
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
- Pratap K. Harbham
- West Midlands Academic Foundation Programme, University of Birmingham, Birmingham, United Kingdom
- Bhuvaneish T. Selvaraj
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
- Bhuvaneish T. Selvaraj
- UK Dementia Research Institute at University of Edinburgh, Edinburgh, United Kingdom
- Bhuvaneish T. Selvaraj
- Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, United Kingdom
- Jenna M. Gregory
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
- Jenna M. Gregory
- UK Dementia Research Institute at University of Edinburgh, Edinburgh, United Kingdom
- Jenna M. Gregory
- Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, United Kingdom
- Jenna M. Gregory
- MRC Edinburgh Brain Bank, Academic Department of Neuropathology, University of Edinburgh, Edinburgh, United Kingdom
- Jenna M. Gregory
- Edinburgh Pathology, University of Edinburgh, Edinburgh, United Kingdom
- Suvankar Pal
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
- Suvankar Pal
- Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, United Kingdom
- Suvankar Pal
- Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, United Kingdom
- Giles E. Hardingham
- UK Dementia Research Institute at University of Edinburgh, Edinburgh, United Kingdom
- Giles E. Hardingham
- Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, United Kingdom
- Giles E. Hardingham
- Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
- Siddharthan Chandran
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
- Siddharthan Chandran
- UK Dementia Research Institute at University of Edinburgh, Edinburgh, United Kingdom
- Siddharthan Chandran
- Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, United Kingdom
- Siddharthan Chandran
- Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, United Kingdom
- Siddharthan Chandran
- Centre for Brain Development and Repair, InStem, Bengaluru, India
- Arpan R. Mehta
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
- Arpan R. Mehta
- UK Dementia Research Institute at University of Edinburgh, Edinburgh, United Kingdom
- Arpan R. Mehta
- Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, United Kingdom
- Arpan R. Mehta
- Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, United Kingdom
- Arpan R. Mehta
- 0Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
- DOI
- https://doi.org/10.3389/fnmol.2021.647895
- Journal volume & issue
-
Vol. 14
Abstract
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.
Keywords
- amyotrophic lateral sclerosis
- cerebrospinal fluid
- motor neuron disease
- neurodegeneration
- pathophysiology
- toxicity