Animal venoms: therapeutic tools for tackling Parkinson’s disease

Amaral, Henrique de Oliveira; Monge-Fuentes, Victoria; Mayer, Andréia Biolchi; Campos, Gabriel Avohay Alves; Lopes, Kamila Soares; Camargo, Luana Cristina; Schwartz, Matheus Ferroni; Galante, Priscilla; Mortari, Márcia Renata

doi:10.1016/j.drudis.2019.09.004

Cited by 12 publications

(4 citation statements)

References 85 publications

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“…Previous works have demonstrated the unique ability of naturally occurring peptides, isolated from animal venom, to interact with intrinsic physiological processes in cells. 6 , 38 , 39 In fact, peptides extracted from the venom of the Conus genus have been reported to have an interestingly anticonvulsant and neuroprotective effect. 40–42 When a comparison was made between Occidentalin-1202(n) and the anticonvulsant peptide, Conantokin-R, isolated from the venom of Conus radiatus , it was found that the peptide isolated in the present study (ED 50 = 1.50 µg/rat or 1.25 nmol/rat) is about 12.5 times less active than Conantokin-R (ED 50 = 0.10 nmol/rat) in the PTZ-induced model of seizures.…”

Section: Discussionmentioning

confidence: 99%

A new class of peptides from wasp venom: a pathway to antiepileptic/neuroprotective drugs

Mortari

Cunha

Anjos

et al. 2022

Brain Communications

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The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation, and purification of Occidentalin-1202(n) from the crude venom, followed by synthesis of an identical analog peptide, named Occidentalin-1202(s). In phase 2, we described the effects of both peptides in two acute models of epilepsy – Kainic acid and pentylenetetrazole-induced model of seizures – and measured estimated ED50 and therapeutic index (TI) values, electroencephalographic studies, and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpine-induced Status epilepticus (SE). After determination of antiepileptic activity of Occidentalin-1202(s), phase 4 consisted of evaluating its potential adverse effects, after chronic administration, on motor coordination (Rotarod) and cognitive impairment (Morris water maze) tests. Finally, in phase 5, we proposed a mechanism of action using computational models with kainate receptors. The new peptide was able to across de blood brain barrier and showed potent antiseizure effects in acute (kainic acid and pentylenetetrazole) and chronic (Temporal Lobe Epilepsy model induced by pilocarpine) models. Motor and cognitive behavior were not adversely affected, and a potential neuroprotective effect was observed. Occidentalin-1202 can be a potent blocker of kainate receptor, as assessed by computational analysis, preventing glutamate and kainic acid from binding to the receptor's active site. Occidentalin-1202 is a peptide with promising applicability to treat epilepsy and can be considered an interesting drug model for the development of new medicines.

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Section: Discussionmentioning

confidence: 99%

A new class of peptides from wasp venom: a pathway to antiepileptic/neuroprotective drugs

Mortari

Cunha

Anjos

et al. 2022

Brain Communications

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“…In addition, around 150 peptides are in active clinical development, and 260 have been tested in human clinical trials [33]. Interestingly, naturally occurring peptides have been proven to exert a range of pharmacological effects, such as neurotrophic, anti-apoptotic, anti-inflammatory and other neuroprotective activities [10].…”

Section: Discussionmentioning

confidence: 99%

“…One interesting peptide that has shown very promising outcomes for the treatment of PD is exendin-4, with several studies demonstrating its potential neuroprotective effect [10]. In fact, exendin-4 has already been addressed in clinical trials for PD treatment, and it was shown to improve patients' motor impairment [34][35][36].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, significant health costs associated with the treatment of PD have resulted in the urgency of finding new therapies for the treatment or prevention of this disease [9]. In this context, compounds isolated from animal venoms have gained great interest in the screening of new therapeutic molecules for the treatment of neurological disorders [10]. The vast repertoire of animal venom molecules have evolved as tools for predation and defense, which have, interestingly, gained the ability to interact directly with vital physiological and biochemical processes into the nervous and cardiovascular systems [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Fraternine, a Novel Wasp Peptide, Protects against Motor Impairments in 6-OHDA Model of Parkinsonism

Biolchi

Oliveira

Amaral

et al. 2020

Toxins

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Parkinson’s disease (PD) is a progressive neurodegenerative condition that affects the Central Nervous System (CNS). Insect venoms show high molecular variability and selectivity in the CNS of mammals and present potential for the development of new drugs for the treatment of PD. In this study, we isolated and identified a component of the venom of the social wasp Parachartergus fraternus and evaluated its neuroprotective activity in the murine model of PD. For this purpose, the venom was filtered and separated through HPLC; fractions were analyzed through mass spectrometry and the active fraction was identified as a novel peptide, called Fraternine. We performed two behavioral tests to evaluate motor discoordination, as well as an apomorphine-induced rotation test. We also conducted an immunohistochemical assay to assess protection in TH+ neurons in the Substantia Nigra (SN) region. Group treated with 10 μg/animal of Fraternine remained longer in the rotarod compared to the lesioned group. In the apomorphine test, Fraternine decreased the number of rotations between treatments. This dose also inhibited dopaminergic neuronal loss, as indicated by immunohistochemical analysis. This study identified a novel peptide able to prevent the death of dopaminergic neurons of the SN and recover motor deficit in a 6-OHDA-induced murine model of PD.

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