TY - JOUR
T1 - 40 Years of CSF Toxicity Studies in ALS
T2 - What Have We Learnt About ALS Pathophysiology?
AU - Ng Kee Kwong, Koy Chong
AU - Harbham, Pratap K.
AU - Selvaraj, Bhuvaneish T.
AU - Gregory, Jenna
AU - Pal, Suvankar
AU - Hardingham, Giles E.
AU - Chandran, Siddharthan
AU - Mehta, Arpan R.
N1 - AM is a Lady Edith Wolfson Clinical Fellow and is jointly funded by the Medical Research Council (MRC) and the Motor Neurone Disease Association (MR/R001162/1). He also acknowledges support from the Rowling Scholars scheme, administered by the Anne Rowling Regenerative Neurology Clinic (ARRNC), University of Edinburgh, and a seedcorn grant from The Chief Scientist Office and the RS Macdonald Charitable Trust via the Scottish Neurological Research Fund, administered by the University of St Andrews. The Hardingham and Chandran laboratories are supported by the Euan MacDonald Centre for Motor Neurone Disease Research, and the UK Dementia Research Institute (DRI), which receives its funding from UK DRI Ltd., funded by the MRC, Alzheimer’s Society and Alzheimer’s Research UK.
PY - 2021/3/18
Y1 - 2021/3/18
N2 - 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.
AB - 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.
KW - amyotrophic lateral sclerosis
KW - , cerebrospinal fluid
KW - motor neuron disease
KW - neurodegeneration
KW - pathophysiology
KW - toxicity
UR - http://dx.doi.org/10.3389/fnmol.2021.647895
U2 - 10.3389/fnmol.2021.647895
DO - 10.3389/fnmol.2021.647895
M3 - Article
VL - 14
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
SN - 1662-5099
M1 - 647895
ER -