Acrolein-mediated injury in nervous system trauma and diseases

Mol Nutr Food Res, 2011 · DOI: 10.1002/mnfr.201100217 · Published: September 1, 2011

Simple Explanation

Acrolein, a reactive aldehyde, is produced in the body during oxidative stress and is also a common pollutant. It is much more reactive and persistent than other similar compounds. Acrolein can overwhelm the body's defenses against oxidative stress, leading to membrane damage, mitochondrial dysfunction, and myelin disruption in nerve cells. Certain drugs, like hydralazine, can bind to acrolein and neutralize its harmful effects, offering a potential treatment strategy for conditions like spinal cord injury and multiple sclerosis.

Study Duration

Not specified

Participants

Animal models of SCI and MS

Evidence Level

Not specified

Key Findings

1
Acrolein is significantly more toxic than other aldehydes like HNE, causing membrane disruption at much lower concentrations.
2
Acrolein impairs mitochondrial respiratory function and increases ROS production in neural tissues.
3
Acrolein exposure leads to myelin disruption, including lengthening of nodes of Ranvier and myelin splitting, affecting nerve signal conduction.

Research Summary

Acrolein, an α,β-unsaturated aldehyde, is a ubiquitous pollutant that is also produced endogenously through lipid peroxidation. Acrolein may overwhelm the anti-oxidative systems of any cell by depleting glutathione reserves, preventing glutathione regeneration, and inactivating protective enzymes. Acrolein scavenging appears to be a novel effective treatment which is primed for rapid translation to the clinic.

Practical Implications

Therapeutic Target

Acrolein is identified as a key therapeutic target for neuroprotection and enhancing functional recovery in neurological disorders.

Drug Repurposing

Hydralazine, an FDA-approved drug, shows promise as an acrolein scavenger and potential treatment for SCI and MS.

Combination Therapy

Combining acrolein scavengers with other treatments like potassium channel blockers may provide better outcomes for neurological injuries.

Study Limitations

1
Concentrations of acrolein in CNS disorders in vivo have not been fully established.
2
Accurate quantification of acrolein is technically challenging due to its rapid reactivity.
3
Limitations of in vitro and ex vivo experiments restrict the duration of acrolein exposure studies.

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