Huntingtin-associated protein 1 ameliorates neurological function rehabilitation by facilitating neurite elongation through TrKA-MAPK pathway in mice spinal cord injury

Frontiers in Molecular Neuroscience, 2023 · DOI: 10.3389/fnmol.2023.1214150 · Published: August 7, 2023

Spinal Cord Injury Neurology Neurorehabilitation

Simple Explanation

This study explores the potential of Huntingtin-associated protein 1 (HAP1) in improving neurological function after spinal cord injury (SCI) in mice. HAP1, a neuronal protein associated with microtubules, might aid in neurological rehabilitation. The research found that HAP1 administration led to improved motor function, pain sensation, warmth sensation, and nerve signal transmission in SCI mice. It also promoted the growth of nerve fibers (neurites) in neural stem cells (NSCs) during their differentiation into neurons. The study identified that HAP1's beneficial effects are linked to the activation of the TrkA-MAPK signaling pathway. This pathway is crucial for nerve growth and regeneration, suggesting that HAP1 enhances recovery after SCI by influencing this pathway.

Study Duration

Not specified

Participants

C57BL/c mice aged approximately 6–8 weeks

Evidence Level

Level Not specified, Original Research

Key Findings

1
Recombinant HAP1 (r-HAP1) improves neurological function rehabilitation after SCI and increases Tuj expression in the injured spinal cord.
2
R-HAP1 enhances neurite growth during neuronal differentiation of NSCs in vitro.
3
HAP1 activates the TrkA-MAPK/ERK signaling pathway, promoting neurite elongation during NSC neuronal differentiation.

Research Summary

This study investigated the therapeutic effects and underlying mechanisms of HAP1 on spinal cord injury in mice. The administration of HAP1 significantly improved neurological function in SCI mice. The research confirmed that r-HAP1 benefits neurite growth on NSCs during neuronal differentiation and axonal regeneration at the injured site of the spinal cord both in vitro and in vivo. The study demonstrated that HAP1 promotes MAPK/ERK phosphorylation through the TrkA signaling pathway, highlighting TrkA's role in HAP1-guided neurite growth.

Practical Implications

Therapeutic Potential

HAP1 could be a potential therapeutic agent for promoting neurological recovery after spinal cord injury.

Signaling Pathway Target

The TrkA-MAPK/ERK signaling pathway represents a key target for interventions aimed at enhancing neurite growth and regeneration.

Drug Development

Development of drugs that mimic or enhance HAP1's activity on the TrkA-MAPK/ERK pathway could lead to improved SCI treatments.

Study Limitations

1
The study only inspected the regeneration of Tuj after HAP1 treatment without further analysis of the ultrastructure of axons.
2
The research did not accomplish the observation that HAP1 is on the differentiation of NSCs.
3
Further studies are needed to explore the long-term effects and potential side effects of HAP1 treatment.

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