Oxidative signaling thresholds shape vulnerability in the central and peripheral nervous systems
- 1Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Abstract
Neurodegeneration is frequently associated with oxidative stress, yet the mechanisms that convert reactive oxygen species (ROS) into irreversible degenerative signals remain incompletely understood. Neurons in the central and peripheral nervous systems often differ in their responses to injury, but these differences cannot be reduced to a simple contrast between weak and strong antioxidant capacity. This Essay proposes that neuronal vulnerability is shaped by multilayered signaling thresholds comprising ROS production, antioxidant and thiol buffering, redox-sensitive signal detection, molecular gating, and commitment to degeneration, survival, or repair. This framework may help explain selective neuronal vulnerability in neurodegenerative diseases and identify intervention points downstream of global ROS suppression.
Neurons in the central nervous system are often more vulnerable to damage during neurodegeneration than neurons in the peripheral nervous system. This Essay argues that differences in how these neurons react to oxidative stress, a major contributor to neurodegenerative disease, could provide a reason why.
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BibTeX
@article{wakatsuki2026oxidative,
title = {{Oxidative signaling thresholds shape vulnerability in the central and peripheral nervous systems}},
author = {Shuji Wakatsuki and Toshiyuki Araki},
journal = {PLOS Biology},
year = {2026},
month = oct,
doi = {10.1371/journal.pbio.3004032},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004032},
note = {CC BY},
}
RIS
TY - JOUR
TI - Oxidative signaling thresholds shape vulnerability in the central and peripheral nervous systems
AU - Shuji Wakatsuki
AU - Toshiyuki Araki
PY - 2026
DA - 2026/10/19
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004032
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004032
AB - Neurodegeneration is frequently associated with oxidative stress, yet the mechanisms that convert reactive oxygen species (ROS) into irreversible degenerative signals remain incompletely understood. Neurons in the central and peripheral nervous systems often differ in their responses to injury, but these differences cannot be reduced to a simple contrast between weak and strong antioxidant capacity. This Essay proposes that neuronal vulnerability is shaped by multilayered signaling thresholds comprising ROS production, antioxidant and thiol buffering, redox-sensitive signal detection, molecular gating, and commitment to degeneration, survival, or repair. This framework may help explain selective neuronal vulnerability in neurodegenerative diseases and identify intervention points downstream of global ROS suppression. Neurons in the central nervous system are often more vulnerable to damage during neurodegeneration than neurons in the peripheral nervous system. This Essay argues that differences in how these neurons react to oxidative stress, a major contributor to neurodegenerative disease, could provide a reason why.
SN - 1545-7885
SN - 1544-9173
ER -