Age-dependent autophagy induction after injury promotes axon regeneration by limiting NOTCH

Autophagy, 2020 · DOI: 10.1080/15548627.2020.1713645 · Published: November 2, 2020

Simple Explanation

This study investigates the role of autophagy in axon regeneration after injury, particularly in the context of aging, using C. elegans as a model. The researchers found that axon injury induces autophagy, which is required for effective axon regeneration by limiting NOTCH signaling. They discovered that the ability of neurons to activate autophagy in response to injury declines with age, but this decline can be partially rescued by autophagy-activating agents.

Study Duration

Not specified

Participants

Caenorhabditis elegans worms

Evidence Level

Not specified

Key Findings

1
Axon injury induces autophagy in neurons, characterized by an increase in autophagosomes and autolysosomes.
2
Injury-triggered autophagy activation and axon regeneration capacity undergo an age-dependent decline.
3
DLK-1 is both required and sufficient for injury-induced autophagy activation.

Research Summary

The study demonstrates that autophagy is essential for axon regeneration, with loss-of-function mutants of autophagy genes displaying impaired axon regeneration. Axon injury induces autophagy in a DLK-1-dependent manner, and this induction declines with age. Enhancing autophagy with drugs like rapamycin can partially rescue the age-dependent decline in axon regrowth. LIN-12/NOTCH, a previously identified inhibitor of axon regeneration, co-localizes with autophagic vesicles, suggesting that autophagy promotes axon regeneration by limiting NOTCH signaling.

Practical Implications

Therapeutic Potential

Activating autophagy may offer a therapeutic strategy for promoting axon regeneration in neurons that lack maximal regrowth capacity, such as in the aged PNS or injured CNS.

Targeting DLK-1

Understanding the role of DLK-1 in injury-induced autophagy could lead to targeted therapies that enhance autophagy and promote axon regeneration.

Modulating NOTCH Signaling

Further research into the relationship between autophagy and NOTCH signaling may reveal new targets for promoting axon regeneration after injury.

Study Limitations

1
The study uses C. elegans as a model, which may not fully translate to mammalian systems.
2
The exact mechanisms by which DLK-1 regulates autophagy require further investigation.
3
The study identifies LIN-12/NOTCH as one target of autophagy, but other targets may also be involved in axon regeneration.

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