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 dis...

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Veröffentlicht in:Neuropeptides (Edinburgh) 2024-02, Vol.103, p.102390-102390, Article 102390
Hauptverfasser: Mayer, Andréia Biolchi, Amaral, Henrique de Oliveira, de Oliveira, Danilo Gustavo R, Campos, Gabriel Avohay Alves, Ribeiro, Priscilla Galante, Fernandes, Solange Cristina Rego, de Souza, Adolfo Carlos Barros, de Castro, Raffael Júnio Araújo, Bocca, Anamélia Lorenzetti, Mortari, Márcia Renata
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Sprache:eng
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Zusammenfassung: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-α, 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-α 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-α levels, making it worthy of consideration for the treatment of PD.
ISSN:0143-4179
1532-2785
DOI:10.1016/j.npep.2023.102390