Why are some neurons spared in neurodegeneration? Cellular subtype identity maintenance as a candidate threshold-setting mechanism
- 1Danish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, Denmark
Abstract
Neurodegenerative diseases often damage some neuronal populations while sparing closely related neighbors. But instead of asking why some neurons die, should we be asking why some survive? This Essay proposes that a neuron’s capacity to sustain the gene-regulatory machinery that maintains its subtype identity helps set the stress threshold beyond which recovery fails. The initiating insult may be metabolic, proteostatic, inflammatory, or arise from the surrounding tissue, but it is the cell’s capacity for maintenance that will determine where the tipping point lies: above a critical level, the identity program recovers, whereas below it, regulatory loss becomes self-sustaining. Such a framing could have implications for how neuronal vulnerability to neurodegeneration is understood.
Why do some neurons die in neurodegenerative disease while closely related neighbors survive? This Essay argues that disease resistance may depend on active maintenance of adult neuronal identity and proposes testable ways to distinguish identity failure from reversible cell-state change.
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BibTeX
@article{kim2026some,
title = {{Why are some neurons spared in neurodegeneration? Cellular subtype identity maintenance as a candidate threshold-setting mechanism}},
author = {Dong Won Kim},
journal = {PLOS Biology},
year = {2026},
month = oct,
doi = {10.1371/journal.pbio.3004014},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004014},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Why are some neurons spared in neurodegeneration? Cellular subtype identity maintenance as a candidate threshold-setting mechanism
AU - Dong Won Kim
PY - 2026
DA - 2026/10/01
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004014
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004014
AB - Neurodegenerative diseases often damage some neuronal populations while sparing closely related neighbors. But instead of asking why some neurons die, should we be asking why some survive? This Essay proposes that a neuron’s capacity to sustain the gene-regulatory machinery that maintains its subtype identity helps set the stress threshold beyond which recovery fails. The initiating insult may be metabolic, proteostatic, inflammatory, or arise from the surrounding tissue, but it is the cell’s capacity for maintenance that will determine where the tipping point lies: above a critical level, the identity program recovers, whereas below it, regulatory loss becomes self-sustaining. Such a framing could have implications for how neuronal vulnerability to neurodegeneration is understood. Why do some neurons die in neurodegenerative disease while closely related neighbors survive? This Essay argues that disease resistance may depend on active maintenance of adult neuronal identity and proposes testable ways to distinguish identity failure from reversible cell-state change.
SN - 1545-7885
SN - 1544-9173
ER -