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  4. Motor function recovery: deciphering a regenerative niche at the neuromuscular synapse

Motor function recovery: deciphering a regenerative niche at the neuromuscular synapse

Biological Reviews, 2021 · DOI: 10.1111/brv.12675 · Published: December 17, 2020

Regenerative MedicineNeurologyGenetics

Simple Explanation

The coordinated movement relies on nerve–muscle communication at the neuromuscular junction (NMJ), a peripheral synapse. The NMJ is composed of a presynaptic motor axon terminal, a postsynaptic muscle specialization, and non-myelinating terminal Schwann cells. We integrate classic and recent evidence describing the cells and molecules that could orchestrate a dynamic ecosystem to accomplish successful NMJ regeneration.

Study Duration
Not specified
Participants
Not specified
Evidence Level
Review

Key Findings

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    A regenerative niche at the mature NMJ must ensure the arrival of regenerating axons to denervated postsynaptic muscle domains for reinnervation.
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    Terminal Schwann cells are essential cells to guide regenerating nerve terminals for successful NMJ repair.
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    Satellite cells in close proximity to regenerating NMJs become preferentially activated and fuse to the muscle fibres after sciatic nerve injury.

Research Summary

This review discusses the cells and molecules involved in establishing a regenerative niche at the neuromuscular junction (NMJ) to promote motor function recovery after injury. It emphasizes the importance of motor axon growth and guidance, maintenance of postsynaptic domain properties, and the roles of terminal Schwann cells and muscle satellite cells in NMJ regeneration. The review highlights potential therapeutic interventions targeting molecules like LRP4, Dok7, MMP3, CXCL12α, and MuSK to improve NMJ regeneration and functional recovery.

Practical Implications

Therapeutic Targets for NMJ Regeneration

Identifies molecules like LRP4, Dok7, MMP3, CXCL12α, and MuSK as potential therapeutic targets for enhancing NMJ regeneration and improving functional recovery after nerve injury or in motor diseases.

Guidance of Motor Axon Growth

The molecular interplay amongst degenerating motor axons and terminal Schwann cells is a highly attractive potential target to manipulate the activation of terminal Schwann cells in order to guide incoming motor axons towards denervated skeletal muscle fibres.

Clinical Relevance in Muscle Transplantation

NMJ regeneration strategies are not only useful after damage or degeneration, but also for muscle transplantation interventions, such as those focused on facial nerve rescue after paralysis, where successful functional NMJ regeneration must also take place.

Study Limitations

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