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

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides Pub Date : 2023-11-13 DOI:10.1016/j.npep.2023.102390

Andréia Biolchi Mayer , Henrique de Oliveira Amaral , Danilo Gustavo R. de Oliveira , Gabriel Avohay Alves Campos , Priscilla Galante Ribeiro , Solange Cristina Rego Fernandes , Adolfo Carlos Barros de Souza , Raffael Júnio Araújo de Castro , Anamélia Lorenzetti Bocca , Márcia Renata Mortari

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引用次数: 0

Abstract

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.

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新的异丙氨酸类似物:帕金森病模型中抗帕金森效应的评价

毒液衍生肽是开发新的治疗分子的重要来源，特别是由于其广泛的药理活性。此前，我们的研究小组发现了一种名为异丙氨酸的新型天然肽，对治疗帕金森病有很好的效果。在本文中，我们合成了三种异丙氨酸生物激发肽:fra-10, fra-14和fra-24。他们在6-羟色胺诱导的帕金森模型中进行测试，量化运动协调性，黑质致密部(SN) TH+神经元水平以及皮层炎症介质TNF-α， IL-6和IL-1ß。肽fra-14和fra-10改善了6-OHDA损伤动物的运动协调性。然而，大多数肽在使用剂量下是有毒的。在阿波啡试验中，所有三种多肽都降低了病变引起的旋转强度。高剂量Fra-24可增加6-OHDA损伤小鼠SN中TH+神经元的数量，降低6-OHDA损伤小鼠皮质中TNF-α的浓度。总的来说，只有肽fra-24对SN多巴胺能神经元有神经保护作用，并能降低细胞因子TNF-α水平，值得考虑用于PD的治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.