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Altered Sphingolipid Hydrolase Activities and Alpha-Synuclein Level in Late-Onset Schizophrenia

Authors :
Tatiana Usenko
Anastasia Bezrukova
Katerina Basharova
Galina Baydakova
Elena Shagimardanova
Nataliya Blatt
Albert Rizvanov
Oleg Limankin
Maxim Novitskiy
Natalia Shnayder
Artem Izyumchenko
Mikhail Nikolaev
Anna Zabotina
Anna Lavrinova
Darya Kulabukhova
Regina Nasyrova
Ekaterina Palchikova
Natalia Zalutskaya
Irina Miliukhina
Yury Barbitoff
Oleg Glotov
Andrey Glotov
Anastasia Taraskina
Nikolai Neznanov
Ekaterina Zakharova
Sofya Pchelina
Source :
Metabolites, Vol 14, Iss 1, p 30 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Recent data described that patients with lysosomal storage disorders (LSDs) may have clinical schizophrenia (SCZ) features. Disruption of lipid metabolism in SCZ pathogenesis was found. Clinical features of schizophrenia (SCZ) have been demonstrated in patients with several lysosomal storage disorders (LSDs). Taking into account the critical role of lysosomal function for neuronal cells’ lysosomal dysfunction could be proposed in SCZ pathogenesis. The current study analyzed lysosomal enzyme activities and the alpha-synuclein level in the blood of patients with late-onset SCZ. In total, 52 SCZ patients with late-onset SCZ, 180 sporadic Parkinson’s disease (sPD) patients, and 176 controls were recruited. The enzymatic activity of enzymes associated with mucopolysaccharidosis (alpha-L-Iduronidase (IDUA)), glycogenosis (acid alpha-glucosidase (GAA)) and sphingolipidosis (galactosylceramidase (GALC), glucocerebrosidase (GCase), alpha-galactosidase (GLA), acid sphingomyelinase (ASMase)) and concentration of lysosphingolipids (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), and lysosphingomyelin (LysoSM)) were measured using LC-MS/MS. The alpha-synuclein level was estimated in magnetically separated CD45+ blood cells using the enzyme-linked immunosorbent assay (ELISA). Additionally, NGS analysis of 11 LSDs genes was conducted in 21 early-onset SCZ patients and 23 controls using the gene panel PGRNseq-NDD. Decreased ASMase, increased GLA activities, and increased HexSpn, LysoGb3, and LysoSM concentrations along with an accumulation of the alpha-synuclein level were observed in late-onset SCZ patients in comparison to the controls (p < 0.05). Four rare deleterious variants among LSDs genes causing mucopolysaccharidosis type I (IDUA (rs532731688, rs74385837) and type III (HGSNAT (rs766835582)) and sphingolipidosis (metachromatic leukodystrophy (ARSA (rs201251634)) were identified in five patients from the group of early-onset SCZ patients but not in the controls. Our findings supported the role of sphingolipid metabolism in SCZ pathogenesis. Aberrant enzyme activities and compounds of sphingolipids associated with ceramide metabolism may lead to accumulation of alpha-synuclein and may be critical in SCZ pathogenesis.

Details

Language :
English
ISSN :
22181989
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
edsdoj.60bfa87fec74cc9b69ac9bb1c5bcca9
Document Type :
article
Full Text :
https://doi.org/10.3390/metabo14010030