Advances in ERK Signaling Pathway in Traumatic Brain Injury: Mechanisms and Therapeutic Potential

Area of Science:

• Neuroscience
• Pathology
• Pharmacology

Background:

• Traumatic brain injury (TBI) is a major cause of death and disability worldwide.
• Secondary injury mechanisms in TBI include oxidative stress, neuroinflammation, apoptosis, and ferroptosis.
• Current TBI treatments lack strategies targeting core pathological pathways.

Purpose of the Study:

• To systematically review the dual roles and molecular mechanisms of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in TBI.
• To examine ERK1/2's involvement in distinct pathological processes post-TBI, such as apoptosis, autophagy, and ferroptosis.
• To summarize the neuroprotective efficacy of ERK-targeting pharmacological agents in TBI animal models.

Main Methods:

• Systematic literature review of studies on ERK1/2 signaling in TBI.
• Analysis of molecular mechanisms underlying ERK1/2's dual roles in TBI pathology.
• Evaluation of preclinical data on ERK-targeting drugs for TBI.

Main Results:

• The ERK1/2 pathway exhibits dual roles in TBI: neuroprotective when activated specifically, but detrimental when hyperactivated.
• ERK1/2 modulates neuronal survival, vascular repair, and glial cell transformation.
• Hyperactivation of ERK1/2 exacerbates oxidative damage, inflammation, and cell death.

Conclusions:

• Precise modulation of ERK1/2 pathway activity offers novel therapeutic strategies for TBI.
• Targeting ERK1/2 presents promising directions for pathological intervention in TBI.
• Pharmacological agents targeting ERK1/2 show neuroprotective efficacy in TBI models.