Nogo limits neural plasticity and recovery from injury

Curr Opin Neurobiol, 2014 · DOI: 10.1016/j.conb.2014.02.011 · Published: August 1, 2014

Simple Explanation

Nogo-A and NgR1, when expressed, restrict the central nervous system's ability to recover from injuries in adult mammals. Nogo-A and NgR1 play a physiological role in limiting experience-dependent plasticity as one matures, which contributes to the stability of synaptic, dendritic, and axonal structures. Neural repair involves plasticity, sprouting and regeneration.

Study Duration

Not specified

Participants

Animal models

Evidence Level

Review article

Key Findings

1
Targeting the Nogo-A/NgR1 pathway has demonstrated effectiveness in promoting functional recovery and neural repair following various CNS injuries, including spinal cord trauma, stroke, and optic nerve damage.
2
The identification of S1PR2 as a receptor for the amino terminal domain of Nogo-A, along with shared signaling components between Nogo-A and CSPGs, expands our understanding of Nogo-A's mechanisms.
3
Interruption of Nogo-A to Nogo-66 Receptor pathway increases functional recovery after injury by a combination of neuronal plasticity, short range sprouting and axonal regeneration.

Research Summary

The Nogo-A and NgR1 signalling cascade have been studied extensively with regard to neurological trauma. Blockade of these pathways leads to greater functional recovery through a combination of neural plasticity, sprouting and axonal regeneration. This pathway limits adult brain plasticity at the level of acute electrophysiological modulation, shown most dramatically in the anatomical stability of synaptic morphology.

Practical Implications

Therapeutic Target

Nogo-A/NgR1 signaling pathway is a potential therapeutic target for promoting neural repair and functional recovery after CNS injuries.

Clinical trials

Early phase clinical trials are in progress for spinal cord injury, MS and ALS using anti-Nogo-A antibodies.

Plasticity Enhancement

Releasing the brakes on anatomical plasticity provides an attractive pathway for neural repair therapeutics.

Study Limitations

1
Compensatory up-regulation of other inhibitory factors may limit the effectiveness of Nogo-A/NgR1 blockade.
2
The higher endogenous growth capacity of Sv129 strain neurons compared to C57Bl6 neurons in these mixed background lines may be an additional confounding factor
3
In optic nerve lesions, the rapid death of retinal ganglion cells and the very low intrinsic growth potential of these neurons complicate the situation.

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