Version 1
: Received: 26 August 2024 / Approved: 27 August 2024 / Online: 28 August 2024 (11:56:48 CEST)
How to cite:
Sinha, P.; Turchyna, Y.; Mitchell, S.; Sadek, M.; Armagan, G.; Perrin, F.; Maesako, M.; Berezovska, O. Glutamate Transporter 1 as a Novel Negative Regulator of Amyloid β. Preprints2024, 2024081982. https://doi.org/10.20944/preprints202408.1982.v1
Sinha, P.; Turchyna, Y.; Mitchell, S.; Sadek, M.; Armagan, G.; Perrin, F.; Maesako, M.; Berezovska, O. Glutamate Transporter 1 as a Novel Negative Regulator of Amyloid β. Preprints 2024, 2024081982. https://doi.org/10.20944/preprints202408.1982.v1
Sinha, P.; Turchyna, Y.; Mitchell, S.; Sadek, M.; Armagan, G.; Perrin, F.; Maesako, M.; Berezovska, O. Glutamate Transporter 1 as a Novel Negative Regulator of Amyloid β. Preprints2024, 2024081982. https://doi.org/10.20944/preprints202408.1982.v1
APA Style
Sinha, P., Turchyna, Y., Mitchell, S., Sadek, M., Armagan, G., Perrin, F., Maesako, M., & Berezovska, O. (2024). Glutamate Transporter 1 as a Novel Negative Regulator of Amyloid β. Preprints. https://doi.org/10.20944/preprints202408.1982.v1
Chicago/Turabian Style
Sinha, P., Masato Maesako and Oksana Berezovska. 2024 "Glutamate Transporter 1 as a Novel Negative Regulator of Amyloid β" Preprints. https://doi.org/10.20944/preprints202408.1982.v1
Abstract
Glutamate transporter-1 (GLT-1) dynamics are implicated in excitotoxicity and Alzheimer's disease (AD) progression. Early stages of AD are often marked by hyperactivity and increased epileptiform activity preceding cognitive decline. Previously, we identified a direct interaction between GLT-1 and Presenilin 1 (PS1) in the brain, highlighting GLT-1 as a promising target in AD research. This study reports the significance of this interaction and uncovers a novel role of GLT-1 in modulating amyloid-beta (Aβ) production. Overexpression of GLT-1 in cells reduces the levels of Aβ40 and Aβ42 by decreasing γ-secretase activity pertinent to APP processing and induces a more "open" PS1 conformation, resulting in decreased Aβ42/40 ratio. Inhibition of the GLT-1/PS1 interaction using cell-permeable peptides produced an opposing effect on Aβ, highlighting the pivotal role of this interaction in regulating Aβ levels. These findings emphasize the potential of targeting GLT-1/PS1 interaction as a novel therapeutic strategy for AD.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
