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Prothymosin α Plays Role as a Brain Guardian through Ecto-F(1) ATPase-P2Y(12) Complex and TLR4/MD2
Prothymosin alpha (ProTα) was discovered to be a necrosis inhibitor from the conditioned medium of a primary culture of rat cortical neurons under starved conditions. This protein carries out a neuronal cell-death-mode switch from necrosis to apoptosis, which is, in turn, suppressed by a variety of...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914670/ https://www.ncbi.nlm.nih.gov/pubmed/36766838 http://dx.doi.org/10.3390/cells12030496 |
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author | Ueda, Hiroshi |
author_facet | Ueda, Hiroshi |
author_sort | Ueda, Hiroshi |
collection | PubMed |
description | Prothymosin alpha (ProTα) was discovered to be a necrosis inhibitor from the conditioned medium of a primary culture of rat cortical neurons under starved conditions. This protein carries out a neuronal cell-death-mode switch from necrosis to apoptosis, which is, in turn, suppressed by a variety of neurotrophic factors (NTFs). This type of NTF-assisted survival action of ProTα is reproduced in cerebral and retinal ischemia–reperfusion models. Further studies that used a retinal ischemia–reperfusion model revealed that ProTα protects retinal cells via ecto-F(1) ATPase coupled with the G(i)-coupled P2Y(12) receptor and Toll-like receptor 4 (TLR4)/MD2 coupled with a Toll–IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF). In cerebral ischemia–reperfusion models, ProTα has additional survival mechanisms via an inhibition of matrix metalloproteases in microglia and vascular endothelial cells. Heterozygous or conditional ProTα knockout mice show phenotypes of anxiety, memory learning impairment, and a loss of neurogenesis. There are many reports that ProTα has multiple intracellular functions for cell survival and proliferation through a variety of protein–protein interactions. Overall, it is suggested that ProTα plays a key role as a brain guardian against ischemia stress through a cell-death-mode switch assisted by NTFs and a role of neurogenesis. |
format | Online Article Text |
id | pubmed-9914670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99146702023-02-11 Prothymosin α Plays Role as a Brain Guardian through Ecto-F(1) ATPase-P2Y(12) Complex and TLR4/MD2 Ueda, Hiroshi Cells Review Prothymosin alpha (ProTα) was discovered to be a necrosis inhibitor from the conditioned medium of a primary culture of rat cortical neurons under starved conditions. This protein carries out a neuronal cell-death-mode switch from necrosis to apoptosis, which is, in turn, suppressed by a variety of neurotrophic factors (NTFs). This type of NTF-assisted survival action of ProTα is reproduced in cerebral and retinal ischemia–reperfusion models. Further studies that used a retinal ischemia–reperfusion model revealed that ProTα protects retinal cells via ecto-F(1) ATPase coupled with the G(i)-coupled P2Y(12) receptor and Toll-like receptor 4 (TLR4)/MD2 coupled with a Toll–IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF). In cerebral ischemia–reperfusion models, ProTα has additional survival mechanisms via an inhibition of matrix metalloproteases in microglia and vascular endothelial cells. Heterozygous or conditional ProTα knockout mice show phenotypes of anxiety, memory learning impairment, and a loss of neurogenesis. There are many reports that ProTα has multiple intracellular functions for cell survival and proliferation through a variety of protein–protein interactions. Overall, it is suggested that ProTα plays a key role as a brain guardian against ischemia stress through a cell-death-mode switch assisted by NTFs and a role of neurogenesis. MDPI 2023-02-02 /pmc/articles/PMC9914670/ /pubmed/36766838 http://dx.doi.org/10.3390/cells12030496 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Ueda, Hiroshi Prothymosin α Plays Role as a Brain Guardian through Ecto-F(1) ATPase-P2Y(12) Complex and TLR4/MD2 |
title | Prothymosin α Plays Role as a Brain Guardian through Ecto-F(1) ATPase-P2Y(12) Complex and TLR4/MD2 |
title_full | Prothymosin α Plays Role as a Brain Guardian through Ecto-F(1) ATPase-P2Y(12) Complex and TLR4/MD2 |
title_fullStr | Prothymosin α Plays Role as a Brain Guardian through Ecto-F(1) ATPase-P2Y(12) Complex and TLR4/MD2 |
title_full_unstemmed | Prothymosin α Plays Role as a Brain Guardian through Ecto-F(1) ATPase-P2Y(12) Complex and TLR4/MD2 |
title_short | Prothymosin α Plays Role as a Brain Guardian through Ecto-F(1) ATPase-P2Y(12) Complex and TLR4/MD2 |
title_sort | prothymosin α plays role as a brain guardian through ecto-f(1) atpase-p2y(12) complex and tlr4/md2 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914670/ https://www.ncbi.nlm.nih.gov/pubmed/36766838 http://dx.doi.org/10.3390/cells12030496 |
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