Interplay of Metallome and Metabolome in Amyotrophic Lateral Sclerosis: A Study on Cerebrospinal Fluid of Patients Carrying Disease-Related Gene Mutations

Nikolay Solovyev, Marianna Lucio, Jessica Mandrioli, Sara Forcisi, Basem Kanawati, Jenny Uhl, Marco Vinceti, Philippe Schmitt-Kopplin, Bernhard Michalke

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a lethal progressive neurodegenerative disease, characterized by a loss of function of upper and lower motor neurons. This study aimed to explore probable pathological alterations occurring in individuals with ALS compared to neurologically healthy controls through the analysis of cerebrospinal fluid (CSF), a medium, which directly interacts with brain parenchyma. A total of 7 ALS patients with disease-associated mutations (ATXN2, C9ORF72, FUS, SOD1, and TARDBP) and 13 controls were included in the study. Multiple analytical approaches were employed, including metabolomic and metallomics profiling, as well as genetic screening, using CSF samples obtained from the brain compartment. Data analysis involved the application of multivariate statistical methods. Advanced hyphenated selenium and redox metal (iron, copper, and manganese) speciation techniques and nontargeted Fourier transform ion cyclotron resonance mass spectrometry-based metabolomics were used for data acquisition. Nontargeted metabolomics showed reduced steroids, including sex hormones; additionally, copper and manganese species were found to be the most relevant features for ALS patients. This indicates a potential alteration of sex hormone pathways in the ALS-affected brain, as reflected in the CSF.

Original languageEnglish
Pages (from-to)3035-3046
Number of pages12
JournalACS Chemical Neuroscience
Volume14
Issue number17
DOIs
Publication statusPublished - 6 Sep 2023
Externally publishedYes

Keywords

  • amyotrophic lateral sclerosis
  • brain steroids
  • disease-related mutations
  • metabolomics
  • metallomics

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