Estrogen Protects Optic Nerve Head Astrocytes Against Oxidative Stress by Preventing Caspase-3 Activation, Tau Dephosphorylation at Ser422 and the Formation of Tau Protein Aggregates
| العنوان: | Estrogen Protects Optic Nerve Head Astrocytes Against Oxidative Stress by Preventing Caspase-3 Activation, Tau Dephosphorylation at Ser422 and the Formation of Tau Protein Aggregates |
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| المؤلفون: | John C. Means, Peter Koulen, Adam A. Lopez |
| المصدر: | Cellular and Molecular Neurobiology. 41:449-458 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Retina, biology, Chemistry, Central nervous system, Tau protein, Caspase 3, Cell Biology, General Medicine, medicine.disease, Retinal ganglion, Cell biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Retinal ganglion cell, medicine, Optic nerve, biology.protein, Cell damage, 030217 neurology & neurosurgery |
| الوصف: | Glaucoma is a neurodegenerative disorder that leads to the slow degeneration of retinal ganglion cells, and results in damage to the optic nerve and concomitant vision loss. As in other disorders affecting the viability of central nervous system neurons, neurons affected by glaucoma do not have the ability to regenerate after injury. Recent studies indicate a critical role for optic nerve head astrocytes (ONHAs) in this process of retinal ganglion cell degeneration. Cleavage of tau, a microtubule stabilizing protein and constituent of neurofibrillary tangles (NFT), plays a major part in the mechanisms that lead to toxicity in CNS neurons and astrocytes. Here, we tested the hypothesis that estrogen, a pleiotropic neuro- and cytoprotectant with high efficacy in the CNS, prevents tau cleavage, and hence, protects ONHAs against cell damage caused by oxidative stress. Our results indicate that estrogen prevents caspase-3 mediated tau cleavage, and thereby decreases the levels of the resulting form of proteolytically cleaved tau protein, which leads to a decrease in NFT formation, which requires proteolytically cleaved tau protein. Overall, our data propose that by stopping the reduction of estrogen levels involved with aging the sensitivity of the optic nerve to glaucomatous damage might be reduced. Furthermore, our data suggest that therapeutic use of estrogen may be beneficial in slowing or preventing the onset or severity of neurodegenerative diseases such as glaucoma and potentially also other degenerative diseases of the CNS through direct control of posttranslational modifications of tau protein. |
| تدمد: | 1573-6830 0272-4340 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::3b1a2ec7d20c4e6bd8a0e385dbbc0f40 https://doi.org/10.1007/s10571-020-00859-6 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........3b1a2ec7d20c4e6bd8a0e385dbbc0f40 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15736830 02724340 |
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