Fungal neurotoxins and sporadic amyotrophic lateral sclerosis

Peter W. French, Russell Ludowyke, Gilles J. Guillemin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We review several lines of evidence that point to a potential fungal origin of sporadic amyotrophic lateral sclerosis (ALS). ALS is the most common form of motor neuron disease (MND) in adults. It is a progressive and fatal disease. Approximately 90% cases of ALS are sporadic, and 5–10% are due to genetic mutations (familial). About 25 genes implicated in familial ALS have been identified so far, including SOD1 and TARDBP, the gene encoding 43 kDa transactive response (TAR) DNA-binding protein (TDP-43). Despite intensive research over many decades, the aetiology of sporadic ALS is still unknown. An environmental cause, including grass or soil-associated fungal infections, is suggested from a range of widely diverse lines of evidence. Clusters of ALS have been reported in soccer players, natives of Guam and farmers. Grass-associated fungi are known to produce a range of neurotoxins and, in symbiotic associations, high levels of fungal SOD1. Exposure of neurons to fungal neurotoxins elicits a significant increase in glutamate production. High levels of glutamate stimulate TDP-43 translocation and modification, providing a link between fungal infection and one of the molecular and histologic hallmarks of sporadic ALS. A recent study provided evidence of a variety of fungi in the cerebrospinal fluid and brain tissue of ALS patients. This review provides a rational explanation for this observation. If a fungal infection could be confirmed as a potential cause of ALS, this could provide a straightforward treatment strategy for this fatal and incurable disease.

LanguageEnglish
Pages969-980
Number of pages12
JournalNeurotoxicity Research
Volume35
Issue number4
Early online date5 Dec 2018
DOIs
Publication statusPublished - 15 May 2019

Fingerprint

Neurotoxins
Amyotrophic Lateral Sclerosis
Mycoses
Fungi
Neurons
Glutamic Acid
Poaceae
Cerebrospinal fluid
Gene encoding
Guam
DNA-Binding Proteins
Motor Neuron Disease
Soccer
Brain
Genes
Population Groups
Tissue
Cerebrospinal Fluid
Soils
Soil

Keywords

  • motor neuron disease
  • amyotrophic lateral sclerosis
  • mycotoxin
  • fungi
  • sporadic ALS

Cite this

French, Peter W. ; Ludowyke, Russell ; Guillemin, Gilles J. / Fungal neurotoxins and sporadic amyotrophic lateral sclerosis. In: Neurotoxicity Research. 2019 ; Vol. 35, No. 4. pp. 969-980.
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Fungal neurotoxins and sporadic amyotrophic lateral sclerosis. / French, Peter W.; Ludowyke, Russell; Guillemin, Gilles J.

In: Neurotoxicity Research, Vol. 35, No. 4, 15.05.2019, p. 969-980.

Research output: Contribution to journalArticleResearchpeer-review

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