SIRT2 Inhibition Improves Functional Motor Recovery After Peripheral Nerve Injury

Neurotherapeutics, 2020 · DOI: https://doi.org/10.1007/s13311-020-00860-3 · Published: April 22, 2020

Simple Explanation

This study investigates the role of Sirtuin-2 (SIRT2) in motor functional recovery after peripheral nerve injury (PNI). SIRT2 is a protein involved in neuroprotection and stress responses. The researchers found that SIRT2 expression increased after nerve injury. They used knockout mice and pharmacological inhibitors to study the effect of blocking SIRT2 activity. Blocking SIRT2 improved functional recovery after sciatic nerve crush in mice. This blockage also increased neurite outgrowth and the levels of certain proteins associated with nerve regeneration.

Study Duration

Not specified

Participants

Wild-type C57BL/6 and SIRT2 KO mice aged 2 months old

Evidence Level

Not specified

Key Findings

1
SIRT2 expression and deacetylase activity increase within motoneurons after axotomy, suggesting a role in motor regeneration.
2
SIRT2 knockout mice exhibit improved functional recovery after sciatic nerve crush, indicating that SIRT2 inhibition is beneficial.
3
SIRT2 blockage enhances p300 acetyltransferase activity, increasing Ac-p53, Ac-H3K9, and GAP43 expression, suggesting an epigenetic mechanism for regeneration.

Research Summary

The study explores the role of SIRT2 in motor functional recovery following peripheral nerve injury (PNI). Results indicate that inhibiting SIRT2 deacetylase activity improves motor functional recovery after PNI. This is linked to increased GAP43 levels within motoneurons, promoting a 'pro-regenerative' neuronal phenotype. The findings suggest that p300-dependent epigenetic mediators facilitate this pro-regenerative state, opening a new therapeutic avenue for ameliorating functional recovery after nervous system injury through epigenetic modifications.

Practical Implications

Therapeutic Target

SIRT2 inhibition may be a viable therapeutic strategy for improving functional recovery after peripheral nerve injury.

Epigenetic Modulation

Bolstering an epigenetic shift that promotes SIRT2 inhibition can be an effective therapy.

Regenerative Medicine

These findings contribute to the understanding of intrinsic mechanisms that can be boosted to improve functional recovery after PNI.

Study Limitations

1
The exact mechanisms by which SIRT2 inhibition promotes functional recovery require further investigation.
2
The study primarily focuses on motor neurons; further research is needed to understand the role of SIRT2 in sensory axons.
3
The long-term effects and potential side effects of SIRT2 inhibition need to be carefully evaluated before clinical application.

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