Discoidin Domain Receptor 1 is a therapeutic target for neurodegenerative diseases
| العنوان: | Discoidin Domain Receptor 1 is a therapeutic target for neurodegenerative diseases |
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| المؤلفون: | Yasar Torres-Yaghi, Jaeil Ahn, Clementina Ullman, Charbel Moussa, Timothy L Chiu, Michaeline Hebron, Christian Wolf, Kaluvu Balaraman, Ethan Weatherdon, Alexander A Missner, Fernando Pagan, Alan J. Fowler, Val Duka, Habtom W. Ressom, Wangke Shi, Xiaoguang Liu, Jonathan D Greenzaid |
| المصدر: | Hum Mol Genet |
| بيانات النشر: | Oxford University Press (OUP), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Lewy Body Disease, Inflammation, Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Discoidin Domain Receptor 1, Alzheimer Disease, Genetics, medicine, Animals, Humans, Receptor, Molecular Biology, Genetics (clinical), 030304 developmental biology, 0303 health sciences, DDR1, Lewy body, Autophagy, Neurodegeneration, Neurodegenerative Diseases, Parkinson Disease, General Medicine, medicine.disease, Vesicular transport protein, Disease Models, Animal, MicroRNAs, Pyrimidines, alpha-Synuclein, Cancer research, General Article, Erratum, medicine.symptom, 030217 neurology & neurosurgery, Discoidin domain |
| الوصف: | The role of Discoidin Domain Receptors (DDRs) is poorly understood in neurodegeneration. DDRs are upregulated in Alzheimer’s and Parkinson’s disease (PD), and DDRs knockdown reduces neurotoxic protein levels. Here we show that potent and preferential DDR1 inhibitors reduce neurotoxic protein levels in vitro and in vivo. Partial or complete deletion or inhibition of DDR1 in a mouse model challenged with α-synuclein increases autophagy and reduces inflammation and neurotoxic proteins. Significant changes of cerebrospinal fluid microRNAs that control inflammation, neuronal injury, autophagy and vesicular transport genes are observed in PD with and without dementia and Lewy body dementia, but these changes are attenuated or reversed after treatment with the DDR1 inhibitor, nilotinib. Collectively, these data demonstrate that DDR1 regulates autophagy and reduces neurotoxic proteins and inflammation and is a therapeutic target in neurodegeneration. |
| تدمد: | 1460-2083 0964-6906 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::075d71d16ec599e5424b1c5668f64defTest https://doi.org/10.1093/hmg/ddaa177Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....075d71d16ec599e5424b1c5668f64def |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602083 09646906 |
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