Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy
Gaucher disease (GD) is the most frequent sphingolipidosis, caused by biallelic pathogenic variants in the <i>GBA1</i> gene encoding for β-glucocerebrosidase (GCase, E.C. 3.2.1.45). The condition is characterized by hepatosplenomegaly, hematological abnormalities, and bone disease in bot...
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MDPI AG
2023-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/4/644 |
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| author | Paweł Dubiela Paulina Szymańska-Rożek Andrzej Eljaszewicz Patryk Lipiński Piotr Hasiński Dorota Giersz Alicja Walewska Marlena Tynecka Marcin Moniuszko Anna Tylki-Szymańska |
| author_facet | Paweł Dubiela Paulina Szymańska-Rożek Andrzej Eljaszewicz Patryk Lipiński Piotr Hasiński Dorota Giersz Alicja Walewska Marlena Tynecka Marcin Moniuszko Anna Tylki-Szymańska |
| author_sort | Paweł Dubiela |
| collection | DOAJ |
| description | Gaucher disease (GD) is the most frequent sphingolipidosis, caused by biallelic pathogenic variants in the <i>GBA1</i> gene encoding for β-glucocerebrosidase (GCase, E.C. 3.2.1.45). The condition is characterized by hepatosplenomegaly, hematological abnormalities, and bone disease in both non-neuronopathic type 1 (GD1) and neuronopathic type 3 (GD3). Interestingly, <i>GBA1</i> variants were found to be one of the most important risk factors for the development of Parkinson’s disease (PD) in GD1 patients. We performed a comprehensive study regarding the two most disease-specific biomarkers, glucosylsphingosine (Lyso-Gb1) and α-synuclein for GD and PD, respectively. A total of 65 patients with GD treated with ERT (47 GD1 patients and 18 GD3 patients), 19 <i>GBA1</i> pathogenic variant carriers (including 10 L444P carriers), and 16 healthy subjects were involved in the study. Lyso-Gb1 was assessed by dried blood spot testing. The level of α-synuclein as an mRNA transcript, total, and oligomer protein concentration were measured with real-time PCR and ELISA, respectively. α-synuclein mRNA level was found significantly elevated in GD3 patients and L444P carriers. GD1 patients, along with <i>GBA1</i> carriers of an unknown or unconfirmed variant, as well as healthy controls, have the same low level of α-synuclein mRNA. There was no correlation found between the level of α-synuclein mRNA and age in GD patients treated with ERT, whereas there was a positive correlation in L444P carriers. |
| first_indexed | 2024-03-11T05:11:40Z |
| format | Article |
| id | doaj.art-0c7ce5d3a985460f9ee8a8057bc41750 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T05:11:40Z |
| publishDate | 2023-04-01 |
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| series | Biomolecules |
| spelling | doaj.art-0c7ce5d3a985460f9ee8a8057bc417502023-11-17T18:29:21ZengMDPI AGBiomolecules2218-273X2023-04-0113464410.3390/biom13040644Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement TherapyPaweł Dubiela0Paulina Szymańska-Rożek1Andrzej Eljaszewicz2Patryk Lipiński3Piotr Hasiński4Dorota Giersz5Alicja Walewska6Marlena Tynecka7Marcin Moniuszko8Anna Tylki-Szymańska9Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, 15-269 Bialystok, PolandFaculty of Mathematics, Informatics and Mechanics, University of Warsaw, 02-097 Warsaw, PolandDepartment of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Pediatrics, Nutrition and Metabolic Diseases, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Internal Medicine and Gastroenterology, Municipal Hospital, 43-100 Tychy, PolandDepartment of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Pediatrics, Nutrition and Metabolic Diseases, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandGaucher disease (GD) is the most frequent sphingolipidosis, caused by biallelic pathogenic variants in the <i>GBA1</i> gene encoding for β-glucocerebrosidase (GCase, E.C. 3.2.1.45). The condition is characterized by hepatosplenomegaly, hematological abnormalities, and bone disease in both non-neuronopathic type 1 (GD1) and neuronopathic type 3 (GD3). Interestingly, <i>GBA1</i> variants were found to be one of the most important risk factors for the development of Parkinson’s disease (PD) in GD1 patients. We performed a comprehensive study regarding the two most disease-specific biomarkers, glucosylsphingosine (Lyso-Gb1) and α-synuclein for GD and PD, respectively. A total of 65 patients with GD treated with ERT (47 GD1 patients and 18 GD3 patients), 19 <i>GBA1</i> pathogenic variant carriers (including 10 L444P carriers), and 16 healthy subjects were involved in the study. Lyso-Gb1 was assessed by dried blood spot testing. The level of α-synuclein as an mRNA transcript, total, and oligomer protein concentration were measured with real-time PCR and ELISA, respectively. α-synuclein mRNA level was found significantly elevated in GD3 patients and L444P carriers. GD1 patients, along with <i>GBA1</i> carriers of an unknown or unconfirmed variant, as well as healthy controls, have the same low level of α-synuclein mRNA. There was no correlation found between the level of α-synuclein mRNA and age in GD patients treated with ERT, whereas there was a positive correlation in L444P carriers.https://www.mdpi.com/2218-273X/13/4/644Gaucher diseaseParkinson’s diseaseglucosylsphingosineα-synucleinenzyme replacement therapy |
| spellingShingle | Paweł Dubiela Paulina Szymańska-Rożek Andrzej Eljaszewicz Patryk Lipiński Piotr Hasiński Dorota Giersz Alicja Walewska Marlena Tynecka Marcin Moniuszko Anna Tylki-Szymańska Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy Biomolecules Gaucher disease Parkinson’s disease glucosylsphingosine α-synuclein enzyme replacement therapy |
| title | Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy |
| title_full | Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy |
| title_fullStr | Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy |
| title_full_unstemmed | Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy |
| title_short | Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy |
| title_sort | alpha synuclein mrna level found dependent on l444p variant in carriers and gaucher disease patients on enzyme replacement therapy |
| topic | Gaucher disease Parkinson’s disease glucosylsphingosine α-synuclein enzyme replacement therapy |
| url | https://www.mdpi.com/2218-273X/13/4/644 |
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