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Solovyev, N. ; Lucio, M. ; Mandrioli, J.* ; Forcisi, S. ; Kanawati, B. ; Uhl, J. ; Vinceti, M.* ; Schmitt-Kopplin, P. ; Michalke, B.

Interplay of metallome and metabolome in amyotrophic lateral sclerosis: A study on cerebrospinal fluid of patients carrying disease-related gene mutations.

ACS Chem. Neurosci. 14, 3035-3046 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Amyotrophic Lateral Sclerosis ; Brain Steroids ; Disease-related Mutations ; Metabolomics ; Metallomics; Alzheimers-disease; Mouse Model; Copper; Selenium; Risk; Iron; Epidemiology; Pesticides; Manganese; Hormones
e-ISSN 1948-7193
Zeitschrift ACS Chemical Neuroscience
Quellenangaben Band: 14, Heft: 17, Seiten: 3035-3046 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Verlagsort 1155 16th St, Nw, Washington, Dc 20036 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit BioGeoChemistry and Analytics (BGC)