{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:15:35Z","timestamp":1782407735677,"version":"3.54.5"},"reference-count":86,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T00:00:00Z","timestamp":1703980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2021-1061"],"award-info":[{"award-number":["075-15-2021-1061"]}]},{"name":"The Ministry of Science and Higher Education of the Russian Federation","award":["RF 193021X0029"],"award-info":[{"award-number":["RF 193021X0029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>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\u2019 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\u2019s 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/metabo14010030","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T10:01:06Z","timestamp":1704016866000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Altered Sphingolipid Hydrolase Activities and Alpha-Synuclein Level in Late-Onset Schizophrenia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-2283","authenticated-orcid":false,"given":"Tatiana","family":"Usenko","sequence":"first","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia"},{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre Kurchatov Institute, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Bezrukova","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies Research Center, Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia"},{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre Kurchatov Institute, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Basharova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. 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Konstantinov of National Research Centre Kurchatov Institute, 188300 Gatchina, Russia"},{"name":"Research Center for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2339-261X","authenticated-orcid":false,"given":"Elena","family":"Shagimardanova","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Blatt","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-5739","authenticated-orcid":false,"given":"Albert","family":"Rizvanov","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"},{"name":"Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, 420111 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Limankin","sequence":"additional","affiliation":[{"name":"Psychiatric Hospital No. 1 Named after P. P. Kashchenko, 195009 Saint Petersburg, Russia"},{"name":"North-Western Medical University Named after P. I.I. Mechnikov of the Ministry of Health of the Russian Federation, 191015 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2001-6432","authenticated-orcid":false,"given":"Maxim","family":"Novitskiy","sequence":"additional","affiliation":[{"name":"Center for Personalized Psychiatry and Neurology of the N.N. V.M. Bekhtereva, 192019 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Shnayder","sequence":"additional","affiliation":[{"name":"Center for Personalized Psychiatry and Neurology of the N.N. V.M. 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