Biochemical and Toxinological Characterization of Venom from Macrorhynchia philippina (Cnidaria, Hydrozoa)

Banagouro, Karine Cristie Quaglio; Viana, Jefferson; Lima, Leonardo Pereira de; Coelho, Guilherme Rabelo; Rocha, Thalita; Girardello, Raquel; Russi, Karolayne Larissa; Kitahara, Marcelo V.; Sciani, Juliana Mozer

doi:10.1155/2022/8170252

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…This peptide was isolated from Merluccius productus fish by Lee et al (2019) and slightly modified by our group to be less charged and suitable to permeation through the blood-brain barrier. This peptide was chosen because it has a similar amino acid sequence and hydrophobicity pattern in peptides characterized by our group [ (Banagouro et al, 2022) and data not shown], with BACE-1 inhibitory activity determined in silico.…”

Section: Discussionmentioning

confidence: 99%

Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1

Boldin,

Zychar,

Gonçalves

et al. 2023

Front. Pharmacol.

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Introduction: Alzheimer’s disease (AD) is the main type of dementia, caused by the accumulation of amyloid plaques, formed by amyloid peptides after being processed from amyloid precursor protein (APP) by γ- and ß-secretases (BACE-1). Although amyloid peptides have been well established for AD, they have been found in other neurodegenerative diseases, such as Parkinson’s disease, Lewy body dementia, and amyotrophic lateral sclerosis. Inhibitors of BACE-1 have been searched and developed, but clinical trials failed due to lack of efficacy or toxicity. Nevertheless, it is still considered a good therapeutic target, as it was proven to remove amyloid peptides and improve memory.Methods: In this work, we designed a peptide based on a sequence obtained from the marine fish Merluccius productus and evaluated it by molecular docking to verify its binding to BACE-1, which was tested experimentally by enzymatic kinetics and cell culture assays. The peptide was injected in healthy mice to study its pharmacokinetics and toxicity.Results: We could obtain a new sequence in which the first N-terminal amino acids and the last one bound to the catalytic site of BACE-1 and showed high stability and hydrophobicity. The synthetic peptide showed a competitive inhibition of BACE-1 and Ki = 94 nM, and when injected in differentiated neurons, it could reduce Aβ42o production. In plasma, its half-life is ∼1 h, clearance is 0.0015 μg/L/h, and Vss is 0.0015 μg/L/h. The peptide was found in the spleen and liver 30 min after injection and reduced its level after that, when it was quantified in the kidneys, indicating its fast distribution and urinary excretion. Interestingly, the peptide was found in the brain 2 h after its administration. Histological analysis showed no morphological alteration in any organ, as well as the absence of inflammatory cells, indicating a lack of toxicity.Discussion: We obtained a new BACE-1 inhibitor peptide with fast distribution to the tissues, without accumulation in any organ, but found in the brain, with the possibility to reach its molecular target, BACE-1, contributing to the reduction in the amyloid peptide, which causes amyloid-linked neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1

Boldin,

Zychar,

Gonçalves

et al. 2023

Front. Pharmacol.

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Tubastrine, an antioxidant molecule from Tubastraea tagusensis sun coral, in the reversion of oxidative stress and neuron's death induced by Aβ42

Silva,

Rostirola,

Speri

et al. 2024

J Cellular Molecular Medi

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder involving mitochondrial dysfunction and consequent production of reactive oxygen species (ROS), generated after amyloid peptide (Aβ42) accumulation. In this study, we isolated a new antioxidant molecule from the sun coral Tubastraea tagusensis and analysed it in cells exposed to oligomeric amyloid‐beta peptide 1‐42 (oAβ42). The coral was collected and immersed in methanol for the release of compounds, which were submitted to antioxidant DPPH and FRAP activity‐guided fractionation using solid‐phase extraction and HPLC. An active pure molecule was analysed by mass spectrometry and tested in SH‐SY5Y differentiated neurons previously exposed to 5 μM oAβ42. The isolated active molecule was identified as tubastrine, which could significantly inhibit the cell death caused by the amyloid peptide. Moreover, oAβ42 increased the percentage of ROS in neurons‐like from 40% to 65%, and the treatment with tubastrine reduced it to 50%. The antioxidant power of neurons‐like after oAβ42 decreased significantly, while the compound reversed it, reaching similar values to the untreated cells. Therefore, tubastrine can reverse an important pathophysiological mechanism of AD, oxidative stress, by increasing neuronal antioxidant power and reducing ROS levels, able to prevent neuron‐like cell death caused by oAβ42.

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Biochemical and Toxinological Characterization of Venom from Macrorhynchia philippina (Cnidaria, Hydrozoa)

Cited by 2 publications

References 43 publications

Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1

Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1

Tubastrine, an antioxidant molecule from Tubastraea tagusensis sun coral, in the reversion of oxidative stress and neuron's death induced by Aβ42

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