RESUMO
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.
Assuntos
Comportamento Animal/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Peptídeos/farmacologia , Substância Negra/efeitos dos fármacos , Venenos de Vespas/química , Animais , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Feminino , Masculino , Camundongos , Degeneração Neural , Fármacos Neuroprotetores/isolamento & purificação , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Peptídeos/isolamento & purificação , Teste de Desempenho do Rota-Rod , Substância Negra/metabolismo , Substância Negra/fisiopatologia , VespasRESUMO
Analgesic therapy is based on the sequential treatment of pain, in which opioids are drugs of last resource and known to be highly effective, but are also responsible for undesirable side effects, tolerance and addiction. There is a need for new drugs with alternative targets in order to minimize side effects and improve treatment efficacy. Mastoparans are an abundant class of peptides in wasp venom and have shown great potential as new drugs, as well as being excellent tools for the study of G-protein-coupled receptors. The objective of this study was to investigate the antinociceptive activity of the mastoparan Agelaia-MP I and the mechanisms involved. Agelaia-MP I (MW 1565 Da) showed dose-dependent antinociceptive activity in mice submitted to i.c.v. injection in two different models. The highest dose produced a maximum effect for up to 4 h, and nociception remained low three days after injection. Further experiments showed that Agelaia-MPI induced partial and reversible blockade of the amplitude of action potential, probably interacting with voltage-gated sodium channels. These results revealed the significant potential impact of compounds isolated from wasp venom on the central nervous system (CNS). In addition, the antinociceptive effect described here is a novel activity for mastoparans.
Assuntos
Analgésicos/farmacologia , Comportamento Animal , Peptídeos/farmacologia , Venenos de Vespas/química , Potenciais de Ação/efeitos dos fármacos , Sequência de Aminoácidos , Analgésicos/administração & dosagem , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Camundongos , Peptídeos/administração & dosagem , Teste de Desempenho do Rota-Rod , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Homologia de Sequência de Aminoácidos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Venenos de Vespas/administração & dosagem , Venenos de Vespas/farmacologia , VespasRESUMO
The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and pathological anxiety.
RESUMO
Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer's Disease, Parkinson's Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis.
Assuntos
Venenos de Abelha/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Venenos de Vespas/uso terapêutico , Animais , Venenos de Abelha/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologia , Venenos de Vespas/farmacologiaRESUMO
The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and pathological anxiety.(AU)
Assuntos
Animais , Venenos de Artrópodes , Produtos Biológicos , Sistema Nervoso Central , Doenças do Sistema NervosoRESUMO
The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimers disease, epilepsy, Parkinsons disease, and pathological anxiety.