Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegeneration
Summary: Drosophila Toll-9 is most closely related to mammalian Toll-like receptors; however, physiological functions of Toll-9 remain elusive. We examined the roles of Toll-9 in fly brains in aging and neurodegeneration. Toll-9 mRNA levels were increased in aged fly heads accompanied by activation...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-02-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000457 |
| _version_ | 1797903376093020160 |
|---|---|
| author | Yasufumi Sakakibara Risa Yamashiro Sachie Chikamatsu Yu Hirota Yoko Tsubokawa Risa Nishijima Kimi Takei Michiko Sekiya Koichi M. Iijima |
| author_facet | Yasufumi Sakakibara Risa Yamashiro Sachie Chikamatsu Yu Hirota Yoko Tsubokawa Risa Nishijima Kimi Takei Michiko Sekiya Koichi M. Iijima |
| author_sort | Yasufumi Sakakibara |
| collection | DOAJ |
| description | Summary: Drosophila Toll-9 is most closely related to mammalian Toll-like receptors; however, physiological functions of Toll-9 remain elusive. We examined the roles of Toll-9 in fly brains in aging and neurodegeneration. Toll-9 mRNA levels were increased in aged fly heads accompanied by activation of nuclear factor-kappa B (NF-kB) and stress-activated protein kinase (SAPK) signaling, and many of these changes were modulated by Toll-9 in glial cells. The loss of Toll-9 did not affect lifespan or brain integrity, whereas it exacerbated hydrogen peroxide-induced lethality. Toll-9 expression was also induced by nerve injury but did not affect acute stress response or glial engulfment activity, suggesting Toll-9 may modulate subsequent neurodegeneration. In a fly tauopathy model, Toll-9 deficiency enhanced neurodegeneration and disease-related tau phosphorylation with reduced SAPK activity, and blocking SAPK enhanced tau phosphorylation and neurodegeneration. In sum, Toll-9 is induced upon aging and nerve injury and affects neurodegeneration by modulating stress kinase signaling. |
| first_indexed | 2024-04-10T09:31:55Z |
| format | Article |
| id | doaj.art-5704f390c4a945dab53244d28a9999a7 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:31:55Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-5704f390c4a945dab53244d28a9999a72023-02-19T04:26:45ZengElsevieriScience2589-00422023-02-01262105968Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegenerationYasufumi Sakakibara0Risa Yamashiro1Sachie Chikamatsu2Yu Hirota3Yoko Tsubokawa4Risa Nishijima5Kimi Takei6Michiko Sekiya7Koichi M. Iijima8Department of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, JapanDepartment of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan; Department of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan; Reseach Fellow of Japan Society for the Promotion of Science, Tokyo, JapanDepartment of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, JapanDepartment of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, JapanDepartment of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, JapanDepartment of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan; Department of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan; Corresponding authorDepartment of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan; Department of Experimental Gerontology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan; Corresponding authorSummary: Drosophila Toll-9 is most closely related to mammalian Toll-like receptors; however, physiological functions of Toll-9 remain elusive. We examined the roles of Toll-9 in fly brains in aging and neurodegeneration. Toll-9 mRNA levels were increased in aged fly heads accompanied by activation of nuclear factor-kappa B (NF-kB) and stress-activated protein kinase (SAPK) signaling, and many of these changes were modulated by Toll-9 in glial cells. The loss of Toll-9 did not affect lifespan or brain integrity, whereas it exacerbated hydrogen peroxide-induced lethality. Toll-9 expression was also induced by nerve injury but did not affect acute stress response or glial engulfment activity, suggesting Toll-9 may modulate subsequent neurodegeneration. In a fly tauopathy model, Toll-9 deficiency enhanced neurodegeneration and disease-related tau phosphorylation with reduced SAPK activity, and blocking SAPK enhanced tau phosphorylation and neurodegeneration. In sum, Toll-9 is induced upon aging and nerve injury and affects neurodegeneration by modulating stress kinase signaling.http://www.sciencedirect.com/science/article/pii/S2589004223000457Biological sciencesNeuroscienceMolecular neuroscience |
| spellingShingle | Yasufumi Sakakibara Risa Yamashiro Sachie Chikamatsu Yu Hirota Yoko Tsubokawa Risa Nishijima Kimi Takei Michiko Sekiya Koichi M. Iijima Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegeneration iScience Biological sciences Neuroscience Molecular neuroscience |
| title | Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegeneration |
| title_full | Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegeneration |
| title_fullStr | Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegeneration |
| title_full_unstemmed | Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegeneration |
| title_short | Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegeneration |
| title_sort | drosophila toll 9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau mediated neurodegeneration |
| topic | Biological sciences Neuroscience Molecular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223000457 |
| work_keys_str_mv | AT yasufumisakakibara drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration AT risayamashiro drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration AT sachiechikamatsu drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration AT yuhirota drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration AT yokotsubokawa drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration AT risanishijima drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration AT kimitakei drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration AT michikosekiya drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration AT koichimiijima drosophilatoll9isinducedbyagingandneurodegenerationtomodulatestresssignalinganditsdeficiencyexacerbatestaumediatedneurodegeneration |