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Tau modulation thro...
Tau modulation through AAV9 therapy augments Akt/Erk survival signalling in glaucoma mitigating the retinal degenerative phenotype
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- Thananthirige, Kanishka Pushpitha Maha (author)
- Macquarie Univ, Australia
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- Chitranshi, Nitin (author)
- Macquarie Univ, Australia
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- Basavarajappa, Devaraj (author)
- Macquarie Univ, Australia
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- Rajput, Rashi (author)
- Macquarie Univ, Australia
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- Abbasi, Mojdeh (author)
- Linköpings universitet,Avdelningen för sinnesorgan och kommunikation,Medicinska fakulteten
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- Palanivel, Viswanthram (author)
- Macquarie Univ, Australia
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- Gupta, Veer Bala (author)
- Deakin Univ, Australia
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- Paulo, Joao A. (author)
- Harvard Med Sch, MA USA
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- Koronyo-Hamaoui, Maya (author)
- Cedars Sinai Med Ctr, CA 90048 USA; Cedars Sinai Med Ctr, CA USA; Cedars Sinai Med Ctr, CA USA
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- Mirzaei, Mehdi (author)
- Macquarie Univ, Australia
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- Graham, Stuart L. (author)
- Macquarie Univ, Australia
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- Gupta, Vivek (author)
- Macquarie Univ, Australia
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(creator_code:org_t)
- BMC, 2024
- 2024
- English.
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In: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 12:1
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The microtubule-associated protein Tau is a key player in various neurodegenerative conditions, including Alzheimer's disease (AD) and Tauopathies, where its hyperphosphorylation disrupts neuronal microtubular lattice stability. Glaucoma, a neurodegenerative disorder affecting the retina, leads to irreversible vision loss by damaging retinal ganglion cells and the optic nerve, often associated with increased intraocular pressure. Prior studies have indicated Tau expression and phosphorylation alterations in the retina in both AD and glaucoma, yet the causative or downstream nature of Tau protein changes in these pathologies remains unclear. This study investigates the impact of Tau protein modulation on retinal neurons under normal and experimental glaucoma conditions. Employing AAV9-mediated gene therapy for Tau overexpression and knockdown, both manipulations were found to adversely affect retinal structural and functional measures as well as neuroprotective Akt/Erk survival signalling in healthy conditions. In the experimental glaucoma model, Tau overexpression intensified inner retinal degeneration, while Tau silencing provided significant protection against these degenerative changes. These findings underscore the critical role of endogenous Tau protein levels in preserving retinal integrity and emphasize the therapeutic potential of targeting Tau in glaucoma pathology.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Glaucoma; Tau; Retinal ganglion cells; Microtubules; Neurodegeneration; Intraocular pressure; Optic nerve
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Thananthirige, K ...
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Chitranshi, Niti ...
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Basavarajappa, D ...
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Rajput, Rashi
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Abbasi, Mojdeh
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Palanivel, Viswa ...
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show more...
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Gupta, Veer Bala
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Paulo, Joao A.
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Koronyo-Hamaoui, ...
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Mirzaei, Mehdi
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Graham, Stuart L ...
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Gupta, Vivek
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Acta neuropathol ...
- By the university
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Linköping University