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Bioprospection of neuroprotective peptides from snake venoms in vitro and in vivo experimental models for the study of neurodegenerative diseases

Abstract

Neurodegenerative diseases promote the progressive loss of different regions of the brain from many molecular and cellular events related to oxidative stress, mitochondrial dysfunction, misfolding of proteins, excitotoxicity, and inflammation. Neuroprotective therapies based on peptides derived from complex natural substances that are capable of improving cell viability or mitochondrial functions as well as delaying or inhibiting the pathogenetic cascade of dysfunctions in neuronal cells are promising and of particular interest to the pharmaceutical industries. Some studies have reported that the low molecular mass fraction and particular peptides from snake venoms have neuroprotective potential against oxidative stress in model experimental in vitro. Further research is clearly needed to discover the details of these agents' neuroprotective mechanisms against reactive oxygen species (ROS)-induced neurotoxicity exerted in an in vivo experimental model, addressing biochemical, molecular, and behavioral parameters. Given the biological complexities of snake venoms from the Elapidae and Viperidae families (I) and the fact that they represent a rich source of biologically active peptides (II) with structural and functional specificities, the goal of this proposal is to conduct bioprospecting of neuroprotective peptides from the venoms of snakes from the Elapidae families (Naja mandalayenses) and (Bothrops jararaca, Daboia siamensis and Lachesis muta), using in vitro (neuronal cell culture) and in vivo (zebrafish with Parkinson's phenotype) experimental models for the study of neurodegenerative diseases and therapeutics. (AU)

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