engleski

Role of HSP70 and HSP90 in motoneuronal death after experimental spinal cord injury.

Spinal cord injury (SCI) is a destructive neurological ailment which results in paralysis or death, and for which no cure exist. Our understanding of molecular and cellular mechanisms underlying pathology of SCI is very poor. However, it is known that after the initial insult, the secondary damage of the spared tissue occurs, in which one of the major mechanism responsible for the death of neurons is excitotoxicity. Excitotoxicity causes death of motoneurons by programmed cell death called parthanatos, characterized by irreversible nuclear chromatin condensation and translocation of apoptosis inducing factor (AIF) to the cell nucleus. One of the protective mechanisms established in motoneurons, to inhibit detrimental effect of AIF, is heat shock response, in which the main role is played by heat shock protein 70 (HSP70). Namely, HSP70 prevents AIF translocation to the cell nucleus by binding it, thus blocking the death cascade leading to parthanatos. In this research, our aim was to study and exploit the potential neuroprotective properties of HSP70, in the in vitro animal model of SCI. We have searched for a way to pharmacologically upregulate HSP70 levels after an experimental SCI. To mimic the excitotoxic SCI, an isolated neonatal rat spinal cord preparation was exposed to kainic acid, a potent glutamate analog. To prevent motoneuronal death we have used celastrol, a natural compound isolated from the plant Tripterygium wilfordii known for its ability to induce the HSP70 expression. Celastrol treatment after the kainateinduced SCI have significantly reduced histological damage of the spinal cord tissue and prevented further death of motoneurons. These results have shown the neuroprotective effects and potential benefits of celastrol to modulate the heat shock response and to reduce the delayed damage after the SCI on rat neonatal SCI model and opened the way for the new strategies to cure SCI based on HSP neuroprotection.

motoneurons, AIF, HSP70, HSP90, celastrol

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