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1.
Neurochem Int ; 136: 104714, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32165170

RESUMO

Neuroinflammation is an important factor contributing to cognitive impairment and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), ischemic injury, and multiple sclerosis (MS). These diseases are characterized by inexorable progressive injury of neuron cells, and loss of motor or cognitive functions. Microglia, which are the resident macrophages in the brain, play an important role in both physiological and pathological conditions. In this review, we provide an updated discussion on the role of ROS and metabolic disease in the pathological mechanisms of activation of the microglial cells and release of cytotoxins, leading to the neurodegenerative process. In addition, we also discuss in vivo models, such as zebrafish and Caenorhabditis elegans, and provide new insights into therapeutics bioinspired by neuropeptides from venomous animals, supporting high throughput drug screening in the near future, searching for a complementary approach to elucidating crucial mechanisms associated with neurodegenerative disorders.


Assuntos
Encéfalo/metabolismo , Doenças Metabólicas/metabolismo , Microglia/metabolismo , Doenças Neurodegenerativas/metabolismo , Animais , Humanos , Macrófagos/metabolismo , Neurônios/metabolismo
2.
Molecules ; 24(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795088

RESUMO

The Indianmeal moth, Plodia interpunctella, is one of the most damaging pests of stored products. We investigated the insecticidal properties of ApKTI, a Kunitz trypsin inhibitor from Adenanthera pavonina seeds, against P. interpunctella larvae through bioassays with artificial diet. ApKTI-fed larvae showed reduction of up to 88% on larval weight and 75% in survival. Trypsin enzymes extracted from P. interpunctella larvae were inhibited by ApKTI, which also demonstrated capacity to bind to chitin. Kinetic studies revealed a non-competitive inhibition mechanism of ApKTI for trypsin, which were further corroborated by molecular docking studies. Furthermore, we have demonstrated that ApKTI exhibits a hydrophobic pocket near the reactive site loop probably involved in chitin interactions. Taken together, these data suggested that the insecticidal activity of ApKTI for P. interpunctella larvae involves a dual and promiscuous mechanisms biding to two completely different targets. Both processes might impair the P. interpunctella larval digestive process, leading to larvae death before reaching the pupal stage. Further studies are encouraged using ApKTI as a biotechnological tool to control insect pests in field conditions.


Assuntos
Fabaceae/química , Inseticidas/química , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Inibidores da Tripsina/química , Inibidores da Tripsina/farmacologia , Animais , Biomassa , Quitina , Inseticidas/isolamento & purificação , Larva , Modelos Moleculares , Conformação Proteica , Sementes/química , Relação Estrutura-Atividade , Tripsina/química , Inibidores da Tripsina/isolamento & purificação
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