PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries

Front Biol (Beijing), 2013 · DOI: 10.1007/s11515-013-1255-1 · Published: August 1, 2013

Simple Explanation

Brain and spinal cord injuries cause damage through cell death. Treatments aim to reduce this damage by interfering with cellular responses through signaling pathways. This review focuses on two key pathways: PTEN/PI3K and MAPK, and how they influence the outcomes of CNS injuries. The PTEN/PI3K pathway, when activated, can promote cell survival and axon regeneration after CNS trauma. Inhibiting PTEN, a key regulator in this pathway, enhances these beneficial effects. MAPK pathways, including Erk, p38, and JNK, play diverse roles in the nervous system. While Erk can promote cell survival, p38 and JNK are often associated with inflammation and cell death after CNS injuries.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Downregulating PTEN promotes axon regeneration and neuroprotection following CNS trauma.
2
Akt phosphorylation decreases within the lesion area following SCI, while increasing in neurons through a PI3K-dependent mechanism within the surrounding injury penumbra.
3
Erk 2 was found to promote white and gray matter tissue loss and functional deficits that were reversed by reduction of the protein after SCI.

Research Summary

Brain and spinal cord injuries initiate widespread temporal and spatial neurodegeneration, through both necrotic and programmed cell death mechanisms. Successful treatments rely on prevention or reduction of the magnitude of disruption, and interfering with injurious cellular responses through modulation of signaling cascades is an effective approach. Current evidence suggests that work toward understanding these complex signaling cascades is not only promising, but may be critical for achieving the goal of improved neurological outcome after brain and spinal cord injuries.

Practical Implications

Therapeutic Targeting of PTEN

Inhibiting PTEN could enhance axon regeneration and neuroprotection after CNS injuries.

Modulation of MAPK Pathways

Selectively modulating MAPK pathways, such as inhibiting JNK and p38 while promoting Erk, may improve outcomes after CNS injuries.

Pharmacological Interventions

Chemical inhibitors targeting PI3K/Akt/mTOR and MAPK pathways can be utilized to assess their roles and benefits in animal models of CNS injury.

Study Limitations

1
Complexities of cellular responses following injury
2
Incomplete understanding of how these pathways are involved in CNS injury and disease
3
Efficacy of Erk activation on neuroprotection is debated

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