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Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration
by
Summers, Daniel W
, Danos, Joseph A
, Addemir, Merve
, McGettigan, Lily
in
Axonogenesis
/ Cell survival
/ Growth factors
/ Nerve growth factor
/ Nervous system
/ Neural networks
/ Neurodegeneration
/ Neuroprotection
/ Neuroscience
/ Neurotrophic factors
/ Phospholipase C
/ TrkA protein
/ TrkA receptors
2025
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Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration
by
Summers, Daniel W
, Danos, Joseph A
, Addemir, Merve
, McGettigan, Lily
in
Axonogenesis
/ Cell survival
/ Growth factors
/ Nerve growth factor
/ Nervous system
/ Neural networks
/ Neurodegeneration
/ Neuroprotection
/ Neuroscience
/ Neurotrophic factors
/ Phospholipase C
/ TrkA protein
/ TrkA receptors
2025
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Do you wish to request the book?
Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration
by
Summers, Daniel W
, Danos, Joseph A
, Addemir, Merve
, McGettigan, Lily
in
Axonogenesis
/ Cell survival
/ Growth factors
/ Nerve growth factor
/ Nervous system
/ Neural networks
/ Neurodegeneration
/ Neuroprotection
/ Neuroscience
/ Neurotrophic factors
/ Phospholipase C
/ TrkA protein
/ TrkA receptors
2025
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Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration
Journal Article
Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration
2025
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Overview
Neurotrophic factors are critical for establishing functional connectivity in the nervous system and sustaining neuronal survival through adulthood. As the first neurotrophic factor purified, nerve growth factor (NGF) is extensively studied for its prolific role in axon outgrowth, pruning, and survival. Applying NGF to diseased neuronal tissue is an exciting therapeutic option and understanding how NGF regulates local axon susceptibility to pathological degeneration is critical for exploiting its full potential. Our study identifies surprising connections between NGF signaling and proteostasis of axon maintenance factors. NGF deprivation increases Nmnat2 and Stmn2 protein levels in axon segments with a corresponding delay in Wallerian degeneration. Conversely, acute NGF stimulation reduces local abundance of these axon maintenance factors and accelerates Wallerian degeneration. Pharmacological studies implicate phospholipase C as the key effector in TrkA activation, which drives degradation of palmitoylated Stmn2. While seemingly opposed to neuroprotective activities well-documented for NGF, downregulating Nmnat2 and Stmn2 favors axonal outgrowth over transient hyper-susceptibility to Sarm1-dependent degeneration. This new facet of NGF biology has important implications for axonal remodeling during development and sustained integrity through adulthood.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
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