New synthetic peptide protects neurons from death induced by toxic influence of activated mast cells via protease-activated receptor

Resumo

The present study focuses on possible ways to protect brain neurons during neuroinflammation. For the first time it is shown that peptide NPNDKYEPF amide, similar to activated protein C (APC), protects hippocampal neurons in a model of neuroinflammation induced by the toxic effects of endotoxin (lipopolysaccharide)-activated mast cells on neurons. It was found that the incubation of hippocampal neurons with mast cells activated by proinflammatory factors leads to neuronal apoptosis within 24 h after the exposure. Preincubation of mast cells with peptide NPNDKYEPF amide or with APC, before the toxin’s treatment, abolishes the toxic effects of the activated mast cells on neurons. By the blockade of protease-activated receptors of type 1 (PAR1), the receptor mechanism of the peptide action on mast cells and on neurons was identified. It was shown that PAR1 is required for the protective effect of the peptide in the conditions of neuroinflammation. Thus, peptide NPNDKYEPF amide is a neuroprotector, similar to APC, and can be used for the development of new approaches of the therapy of inflammatory processes accompanying different types of traumatic and ischemic brain damage.