New fraternine analogues: Evaluation of the antiparkinsonian effect in the model of Parkinson's disease

Venom-derived peptides are important sources for the development of new therapeutic molecules, especially due to their broad pharmacological activity. Previously, our research group identified a novel natural peptide, named fraternine, with promising effects for the treatment of Parkinson's disease. In the present paper, we synthesized three peptides bioinspired in fraternine: fra-10, fra-14, and fra-24. They were tested in the 6-OHDA-induced model of parkinsonism, quantifying motor coordination, levels of TH+ neurons in the substantia nigra pars compacta (SN), and inflammation mediators TNF-alpha, IL-6, and IL-1ss in the cortex. Peptides fra-14 and fra-10 improved the motor coordination in relation to 6-OHDA lesioned animals. However, most of the peptides were toxic in the doses applied. All three peptides reduced the intensity of the lesion induced rotations in the apomorphine test. Fra-24 higher dose increased the number of TH+ neurons in SN and reduced the concentration of TNF-alpha in the cortex of 6-OHDA lesioned mice. Overall, only the peptide fra-24 presented a neuroprotection effect on dopaminergic neurons of SN and a reduction of cytokine TNF-alpha levels, making it worthy of consider-ation for the treatment of PD.

Automated summary

This study synthesized three bioinspired peptides based on fraternine and tested their effects in a Parkinson's disease model. The peptides fra-10 and fra-14 improved motor coordination, but most of the peptides were toxic at the applied doses. All three peptides reduced the intensity of lesion-induced rotations. The peptide fra-24 increased the number of TH+ neurons in the substantia nigra and reduced the concentration of the cytokine TNF-alpha, suggesting it has neuroprotective effects in Parkinson's disease.