Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury

Frontiers in Neuroscience, 2017 · DOI: 10.3389/fnins.2017.00079 · Published: February 21, 2017

Simple Explanation

Injury to axons in the CNS and PNS causes changes in the levels of many molecules involved in nerve repair or damage. Chaperone proteins, which help other proteins fold correctly, often show altered expression after CNS and PNS damage. These proteins generally play a protective role, such as helping damaged neurons survive, promoting axon regeneration and remyelination, and improving behavioral outcomes. Chaperone proteins assist in the correct non-covalent assembly of polypeptides. They recognize unfolded or partially denatured proteins and prevent incorrect associations and aggregation of unfolded polypeptide chains. Some chaperones also affect inflammatory responses or cell survival. Hsps were one of the earliest chaperones discovered to have altered expression after PNS and CNS axonal damage. Subsequent studies have also noted increased expression of other hsps including HSP25 and HSP27. The expression of various chaperones and co-chaperones is altered after CNS and PNS axon damage in either an enhanced or reduced manner.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
HSP27 upregulation and phosphorylation are required for injured sensory and motor neuron survival after sciatic nerve transection.
2
Clusterin is important for regrowth of sensory neurons after sciatic nerve transection and crush injury.
3
AlphaB-crystallin (αBC) contributes to remyelination in the PNS after sciatic nerve crush through a neuregulin 1 Type III/AKT/ErbB2 mechanism.

Research Summary

Following damage to the axons of central nervous system (CNS) and peripheral nervous system (PNS) neurons, a number of cellular and molecular processes are initiated to promote regeneration of damaged nerve ﬁbers, remyelination and target reinnervation. Hsps were one of the earliest chaperones discovered to have altered expression after PNS and CNS axonal damage. Altogether then, the expression of various chaperones and co-chaperones is altered after CNS and PNS axon damage in either an enhanced or reduced manner. Numerous studies over the past three decades have shown that the expression of chaperone proteins are not only altered following nerve damage to CNS and PNS neurons but that these proteins play an active role in the repair processes and in mediating some of the pathological events.

Practical Implications

Therapeutic Potential

Harnessing the protective properties of chaperone proteins could enhance repair after CNS and PNS nerve injury.

Targeted Therapies

Developing therapies that selectively modulate chaperone protein function could promote neuronal survival, axon regeneration, and remyelination.

Pain Management

Understanding the role of chaperones like σ1R in neuropathic pain may lead to new strategies for pain management after nerve injury.

Study Limitations

1
The review highlights the complexity of chaperone protein function after nerve injury, with some promoting repair while others mediate undesirable effects.
2
Further research is needed to clarify the specific mechanisms by which chaperone proteins influence ER stress and autophagy-induced cell death after nerve damage.
3
More research is needed to understand the function(s) chaperone proteins play in the protective PNS immune response as opposed to the slow, limited and seemingly detrimental inﬂammation seen after CNS axotomy.

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