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 M.
AU - Pal, Suvankar
AU - Hardingham, Giles E.
AU - Chandran, Siddharthan
AU - Mehta, Arpan R.
N1 - Copyright:
© 2021 Ng Kee Kwong, Harbham, Selvaraj, Gregory, Pal, Hardingham, Chandran and Mehta.
PY - 2021
Y1 - 2021
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 - https://www.scopus.com/record/display.uri?eid=2-s2.0-85103494336&origin=inward
U2 - 10.3389/fnmol.2021.647895
DO - 10.3389/fnmol.2021.647895
M3 - Review article
C2 - 33815058
SN - 1662-5099
VL - 14
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 647895
ER -