ArticleProceedings of the National Academy of Sciences of the United States of America2018
Palmitoylation enables MAPK-dependent proteostasis of axon survival factors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 88 citations in OpenAlex.
- Combinatorial chemistry identifies additional compounds that selectively inhibit DLK-dependent retrograde signaling while minimally affecting other axonal roles of DLK.Scientific reports · 2026Article
- Gene signatures of palmitoylation and fatty acid metabolism predict prognosis and immunotherapy response in breast cancer patients by machine learning, single-cell analysis, and experimental validation.Frontiers in pharmacology · 2026Article
- In-feedFrontiers in physiology · 2026Article
- MKK4 and MKK7 control degeneration of retinal ganglion cell somas and axons after glaucoma-relevant injury.Cell death discovery · 2025Article
- Tubulin regulates stability and localization of STMN2 by binding preferentially to its soluble form.The Journal of cell biology · 2025Article
- Unveiling the Hidden Impact: Hematoma Volumes Unravel Circuit Disruptions in Intracerebral Hemorrhage.Translational stroke research · 2025Article
- Fat traffic control: S-acylation in axonal transport.Molecular pharmacology · 2025Review
- Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibiting acute, axonal DLK palmitoylation is neuroprotective and avoids deleterious effects of cell-wide DLK inhibition.Nature communications · 2025Article
- Nerve growth factor signaling tunes axon maintenance protein abundance and kinetics of Wallerian degeneration.Molecular biology of the cell · 2025Article
- Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration.bioRxiv : the preprint server for biology · 2025Article
- Influence of palmitoylation in axonal transport mechanisms in neurodegenerative diseases.Frontiers in cellular neuroscience · 2025Review
- Remyelination protects neurons from DLK-mediated neurodegeneration.Nature communications · 2024Article
- Microtubules, Membranes, and Movement: New Roles for Stathmin-2 in Axon Integrity.Journal of neuroscience research · 2024Review
- Remyelination protects neurons from DLK-mediated neurodegeneration.bioRxiv : the preprint server for biology · 2024Article
- SARM1-Dependent Axon Degeneration: Nucleotide Signaling, Neurodegenerative Disorders, Toxicity, and Therapeutic Opportunities.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- NMNAT2 is a druggable target to drive neuronal NAD production.Nature communications · 2024Article
- Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation.Nature neuroscience · 2024Article
- Genetic ablation of Sarm1 attenuates expression and mislocalization of phosphorylated TDP-43 after mouse repetitive traumatic brain injury.Acta neuropathologica communications · 2023Article
- NADAntioxidants & redox signaling · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Axon degeneration is a prominent event in many neurodegenerative disorders. Axon injury stimulates an intrinsic self-destruction program that culminates in activation of the prodegeneration factor SARM1 and local dismantling of damaged axon segments. In healthy axons, SARM1 activity is restrained by constant delivery of the axon survival factor NMNAT2. Elevating NMNAT2 is neuroprotective, while loss of NMNAT2 evokes SARM1-dependent axon degeneration. As a gatekeeper of axon survival, NMNAT2 abundance is an important regulatory node in neuronal health, highlighting the need to understand the mechanisms behind NMNAT2 protein homeostasis. We demonstrate that pharmacological inhibition of the MAP3Ks dual leucine zipper kinase (DLK) and leucine zipper kinase (LZK) elevates NMNAT2 abundance and strongly protects axons from injury-induced degeneration. We discover that MAPK signaling selectively promotes degradation of palmitoylated NMNAT2, as well as palmitoylated SCG10. Conversely, nonpalmitoylated NMNAT2 is degraded by the Phr1/Skp1a/Fbxo45 ligase complex. Combined inactivation of both pathways leads to synergistic accumulation of NMNAT2 in axons and dramatically enhanced protection against pathological axon degeneration. Hence, the subcellular localization of distinct pools of NMNAT2 enables differential regulation of NMNAT2 abundance to control axon survival.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.