Corrected speciation and gyromitrin content of false morels linked to ALS patients with mostly slow-acetylator phenotypes

Emmeline Lagrange ¹, Marie-Anne Loriot ², Nirmal K Chaudhary ³

¹Department of Neurology, Reference Center of Neuromuscular Disease and ALS Consultations, Grenoble University Hospital, Grenoble, France.
²Department of Clinical Chemistry, European Georges-Pompidou hospital, Assistance Publique-Hôpitaux de Paris, University Paris Cité, INSERM UMR-S1138, Centre de Recherches des Cordeliers, 75908 Paris Cedex 15, France.
³Natural Products Discovery Core, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
⁴Department of Ecology and Evolution, University of Michigan, Ann Arbor, MI 48109, USA.
⁵Laboratoire de Biochimie et Biologie Moleculaire, CHU Nimes, Nimes, Motoneuron Disease: Pathophysiology and Therapy, INM, Univ. Montpellier, Montpellier, France.
⁶Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA.
⁷Unité de Recherche Aliments Bioprocédés Toxicologie Environnements (ABTE) EA 4651, Normandie University, UNICAEN, 14000 Caen, France.
⁸NM, Université Montpellier, INSERM, CNRS, Montpellier, France.
⁹Natural Products Discovery Core, Life Sciences Institute, University of Michigan, 48109, USA.
¹⁰Oregon Health & Science University, Portland, OR 97239, USA.

⁰Department of Neurology, Reference Center of Neuromuscular Disease and ALS Consultations, Grenoble University Hospital, Grenoble, France.

Eneurologicalsci +

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May 21, 2024

View abstract on PubMed

Summary

Consumption of toxic wild fungi, specifically false morels like Gyromitra venenata and Gyromitra esculenta, is linked to amyotrophic lateral sclerosis (ALS). These fungi contain high gyromitrin levels, increasing neurotoxic and genotoxic risks, especially for slow acetylator individuals.

Area Of Science

Neuroscience
Toxicology
Mycology

Background

Sporadic amyotrophic lateral sclerosis (ALS) etiology remains largely unknown.
A previous study suggested a link between ALS and wild mushroom consumption in the French Alps.
The specific fungal species and toxins involved were not definitively identified.

Purpose Of The Study

To identify the specific species of wild fungi associated with ALS cases in a French Alpine village.
To investigate the toxicological properties of these fungi and their potential role in ALS pathogenesis.
To explore the influence of host genetic factors, specifically N-acetyltransferase-2 (NAT2) phenotype, on ALS risk.

Main Methods

Case-control study design involving ALS patients and controls from a French Alpine village.
Expert mycological re-examination of fungal specimens consumed by ALS patients.
Chemical analysis of gyromitrin content in identified fungal species.
N-acetyltransferase-2 (NAT2) genotyping of ALS patients to determine acetylator phenotype.

Main Results

ALS cases were associated with the consumption of wild fungi misidentified as Gyromitra gigas.
Re-examination identified the fungi as Gyromitra venenata and Gyromitra esculenta, species with high gyromitrin concentrations.
Gyromitrin is metabolized to monomethylhydrazine, a known neurotoxin and genotoxin.
A majority of ALS patients exhibited slow or intermediate NAT2 acetylator phenotypes, increasing susceptibility to gyromitrin's toxic effects.

Conclusions

Consumption of specific false morel species (Gyromitra venenata, G. esculenta) containing high gyromitrin levels is a potential environmental risk factor for sporadic ALS.
The neurotoxic and genotoxic effects of gyromitrin metabolites, exacerbated by slow NAT2 acetylation, may contribute to ALS pathogenesis.
Further research is warranted to confirm the role of these fungi and associated toxins in ALS etiology.

Keywords:

Amyotrophic lateral sclerosis False morels Genotoxicity Gyromitrin NAT2 genotype

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