TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy
Lafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy (prevalence <1:1,000,000) characterized by the accumulation of insoluble deposits of aberrant glycogen (polyglucosans), named Lafora bodies, in the brain but also in peripheral tissues. LD is the most severe form of...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122003564 |
| _version_ | 1797978298082394112 |
|---|---|
| author | Teresa Rubio Rosa Viana Mireia Moreno-Estellés Ángela Campos-Rodríguez Pascual Sanz |
| author_facet | Teresa Rubio Rosa Viana Mireia Moreno-Estellés Ángela Campos-Rodríguez Pascual Sanz |
| author_sort | Teresa Rubio |
| collection | DOAJ |
| description | Lafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy (prevalence <1:1,000,000) characterized by the accumulation of insoluble deposits of aberrant glycogen (polyglucosans), named Lafora bodies, in the brain but also in peripheral tissues. LD is the most severe form of the group of progressive myoclonus epilepsies, since patients present a rapid deterioration and dementia with amplification of seizures, leading to death after a decade from the onset of the first symptoms. We have recently described that reactive glia-derived neuroinflammation should be considered a novel hallmark of LD since we observed a florid upregulation of differentially expressed genes in both LD mouse lines, which were mainly related to mediators of inflammatory response. In this work, we define an upregulation of the expression of mediators of the TNF and IL6/JAK2 signaling pathways in LD. In addition, we describe the activation of the non-canonical form of the inflammasome. Furthermore, we describe the infiltration of peripheral immune cells in the brain parenchyma, which could aggravate glia-derived neuroinflammation. Finally, we describe CXCL10 and S100b as blood biomarkers of the disease, which will allow the study of the progression of the disease using serum blood samples. We consider that the identification of these initial inflammatory changes in LD will be very important to implement possible anti-inflammatory therapeutic strategies to prevent the development of the disease. |
| first_indexed | 2024-04-11T05:20:30Z |
| format | Article |
| id | doaj.art-8b995996921a47c5abe54c94aa491382 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-11T05:20:30Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-8b995996921a47c5abe54c94aa4913822022-12-24T04:50:23ZengElsevierNeurobiology of Disease1095-953X2023-01-01176105964TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsyTeresa Rubio0Rosa Viana1Mireia Moreno-Estellés2Ángela Campos-Rodríguez3Pascual Sanz4Instituto de Biomedicina de Valencia, CSIC, Jaime Roig 11, 46010 Valencia, SpainInstituto de Biomedicina de Valencia, CSIC, Jaime Roig 11, 46010 Valencia, SpainInstituto de Biomedicina de Valencia, CSIC, Jaime Roig 11, 46010 Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain.Instituto de Biomedicina de Valencia, CSIC, Jaime Roig 11, 46010 Valencia, SpainInstituto de Biomedicina de Valencia, CSIC, Jaime Roig 11, 46010 Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain.; Corresponding author at: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Jaime Roig 11, 46010, Valencia, Spain.Lafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy (prevalence <1:1,000,000) characterized by the accumulation of insoluble deposits of aberrant glycogen (polyglucosans), named Lafora bodies, in the brain but also in peripheral tissues. LD is the most severe form of the group of progressive myoclonus epilepsies, since patients present a rapid deterioration and dementia with amplification of seizures, leading to death after a decade from the onset of the first symptoms. We have recently described that reactive glia-derived neuroinflammation should be considered a novel hallmark of LD since we observed a florid upregulation of differentially expressed genes in both LD mouse lines, which were mainly related to mediators of inflammatory response. In this work, we define an upregulation of the expression of mediators of the TNF and IL6/JAK2 signaling pathways in LD. In addition, we describe the activation of the non-canonical form of the inflammasome. Furthermore, we describe the infiltration of peripheral immune cells in the brain parenchyma, which could aggravate glia-derived neuroinflammation. Finally, we describe CXCL10 and S100b as blood biomarkers of the disease, which will allow the study of the progression of the disease using serum blood samples. We consider that the identification of these initial inflammatory changes in LD will be very important to implement possible anti-inflammatory therapeutic strategies to prevent the development of the disease.http://www.sciencedirect.com/science/article/pii/S0969996122003564Lafora diseaseAstrocytesMicrogliaNeuroinflammationTNFIL6 |
| spellingShingle | Teresa Rubio Rosa Viana Mireia Moreno-Estellés Ángela Campos-Rodríguez Pascual Sanz TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy Neurobiology of Disease Lafora disease Astrocytes Microglia Neuroinflammation TNF IL6 |
| title | TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy |
| title_full | TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy |
| title_fullStr | TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy |
| title_full_unstemmed | TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy |
| title_short | TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy |
| title_sort | tnf and il6 jak2 signaling pathways are the main contributors of the glia derived neuroinflammation present in lafora disease a fatal form of progressive myoclonus epilepsy |
| topic | Lafora disease Astrocytes Microglia Neuroinflammation TNF IL6 |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122003564 |
| work_keys_str_mv | AT teresarubio tnfandil6jak2signalingpathwaysarethemaincontributorsofthegliaderivedneuroinflammationpresentinlaforadiseaseafatalformofprogressivemyoclonusepilepsy AT rosaviana tnfandil6jak2signalingpathwaysarethemaincontributorsofthegliaderivedneuroinflammationpresentinlaforadiseaseafatalformofprogressivemyoclonusepilepsy AT mireiamorenoestelles tnfandil6jak2signalingpathwaysarethemaincontributorsofthegliaderivedneuroinflammationpresentinlaforadiseaseafatalformofprogressivemyoclonusepilepsy AT angelacamposrodriguez tnfandil6jak2signalingpathwaysarethemaincontributorsofthegliaderivedneuroinflammationpresentinlaforadiseaseafatalformofprogressivemyoclonusepilepsy AT pascualsanz tnfandil6jak2signalingpathwaysarethemaincontributorsofthegliaderivedneuroinflammationpresentinlaforadiseaseafatalformofprogressivemyoclonusepilepsy |