Myelin basic protein enhances axonal regeneration from neural progenitor cells

Cell Biosci, 2021 · DOI: https://doi.org/10.1186/s13578-021-00584-7 · Published: April 1, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study explores how myelin, a substance that insulates nerve fibers, affects the regrowth of nerve fibers from neural progenitor cells (NPCs) after spinal cord injury (SCI). The researchers focused on myelin basic protein (Mbp), a component of myelin. They found that Mbp promotes the growth of nerve fibers from NPCs. This process involves Mbp's interaction with L1cam to produce L1-70, which then activates PPARγ. This activation represses genes that inhibit nerve cell differentiation and enhances Erk1/2 activation, further supporting nerve fiber growth. In mice with SCI, NPCs modified to overproduce Mbp showed improved recovery and nerve regeneration, suggesting that this approach could be a new way to treat SCI.

Study Duration

12 weeks (in vivo)

Participants

Murine dorsal column crush model of SCI

Evidence Level

Not specified

Key Findings

1
Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner, indicating Mbp's crucial role in this process.
2
Mbp's stimulatory effects on NPC neurite outgrowth are mediated by Mbp's production of L1-70, highlighting the importance of this cleavage product.
3
Mbp/L1-70's stimulatory effects on NPC neurite outgrowth are mediated by PPARγ, establishing PPARγ as a key downstream mediator.

Research Summary

The study identifies Mbp as a key gene in myelin-associated NPC axonal regeneration, based on bioinformatics analysis. In vivo experiments showed that Mbp-overexpressing NPCs enhanced locomotive recovery and axonal regeneration in post-SCI mice. The research elucidates a novel Mbp/L1cam/Pparγ signaling pathway through which Mbp supports axonal regeneration from mammalian NPCs.

Practical Implications

Therapeutic Target

Mbp and its downstream signaling pathway (L1cam/PPARγ) represent potential therapeutic targets for promoting axonal regeneration in SCI.

Bioengineered Interventions

NPC-based interventions bioengineered to overexpress Mbp could be a promising approach for promoting functional recovery post-SCI.

Drug Development

Small molecules that mimic or enhance the activity of Mbp or its downstream targets could be developed as potential SCI therapies.

Study Limitations

1
The study acknowledges the possibility of other myelin-associated proteins significantly impacting neurite outgrowth beyond Mbp.
2
The focus on PPARγ activity as a key regulator might overlook other downstream targets of the Mbp/L1-70 axis that could influence neurite outgrowth.
3
Although Mbp knockout produced profound neurite growth reductions in NPCs cultured on myelin, it is reasonable to assume that there may be other myelin-associated proteins that significantly impact neurite outgrowth.

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