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Axon injury induced endoplasmic reticulum stress and neurodegeneration

Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury often leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although t...

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Autor principal: Hu, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116825/
https://www.ncbi.nlm.nih.gov/pubmed/27904477
http://dx.doi.org/10.4103/1673-5374.193225
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author Hu, Yang
author_facet Hu, Yang
author_sort Hu, Yang
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description Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury often leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although these sequential events are clearly connected, ample evidence indicates that neuronal soma and axon degenerations are active autonomous processes with distinct molecular mechanisms. By exploiting the anatomical and technical advantages of the retinal ganglion cell (RGC)/optic nerve (ON) system, we demonstrated that inhibition of the PERK-eIF2α-CHOP pathway and activation of the X-box binding protein 1 pathway synergistically protect RGC soma and axon, and preserve visual function, in both acute ON traumatic injury and chronic glaucomatous neuropathy. The autonomous endoplasmic reticulum (ER) stress pathway in neurons has been implicated in several other neurodegenerative diseases. In addition to the emerging role of ER morphology in axon maintenance, we propose that ER stress is a common upstream signal for disturbances in axon integrity, and that it leads to a retrograde signal that can subsequently induce neuronal soma death. Therefore manipulation of the ER stress pathway may be a key step toward developing the effective neuroprotectants that are greatly needed in the clinic.
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spelling pubmed-51168252016-11-30 Axon injury induced endoplasmic reticulum stress and neurodegeneration Hu, Yang Neural Regen Res Invited Review Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury often leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although these sequential events are clearly connected, ample evidence indicates that neuronal soma and axon degenerations are active autonomous processes with distinct molecular mechanisms. By exploiting the anatomical and technical advantages of the retinal ganglion cell (RGC)/optic nerve (ON) system, we demonstrated that inhibition of the PERK-eIF2α-CHOP pathway and activation of the X-box binding protein 1 pathway synergistically protect RGC soma and axon, and preserve visual function, in both acute ON traumatic injury and chronic glaucomatous neuropathy. The autonomous endoplasmic reticulum (ER) stress pathway in neurons has been implicated in several other neurodegenerative diseases. In addition to the emerging role of ER morphology in axon maintenance, we propose that ER stress is a common upstream signal for disturbances in axon integrity, and that it leads to a retrograde signal that can subsequently induce neuronal soma death. Therefore manipulation of the ER stress pathway may be a key step toward developing the effective neuroprotectants that are greatly needed in the clinic. Medknow Publications & Media Pvt Ltd 2016-10 /pmc/articles/PMC5116825/ /pubmed/27904477 http://dx.doi.org/10.4103/1673-5374.193225 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Invited Review
Hu, Yang
Axon injury induced endoplasmic reticulum stress and neurodegeneration
title Axon injury induced endoplasmic reticulum stress and neurodegeneration
title_full Axon injury induced endoplasmic reticulum stress and neurodegeneration
title_fullStr Axon injury induced endoplasmic reticulum stress and neurodegeneration
title_full_unstemmed Axon injury induced endoplasmic reticulum stress and neurodegeneration
title_short Axon injury induced endoplasmic reticulum stress and neurodegeneration
title_sort axon injury induced endoplasmic reticulum stress and neurodegeneration
topic Invited Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116825/
https://www.ncbi.nlm.nih.gov/pubmed/27904477
http://dx.doi.org/10.4103/1673-5374.193225
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