☆ 4.2 Article

Octovespin, a peptide bioinspired by wasp venom, prevents cognitive deficits induced by amyloid-β in Alzheimer's disease mouse model

NEUROPEPTIDES (2022)

Journal

NEUROPEPTIDES

Volume 93, Issue -, Pages -

Publisher

ELSEVIER

DOI: 10.1016/j.npep.2022.102233

Keywords

Alzheimer's disease; Wasp peptides; Neuroprotective; Amyloid-beta aggregation

Funding

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico -CNPq [428908/2018-7, 306547/2020-1, 403543/2021-5]
Fundacao de Empreendimentos Cientificos e Tecnologicos - FINATEC
Fundacao de Apoio a Pesquisa do Distrito Federal -FAPDF [193.000.539/2009, 00193-00000724/2021-30, 00193-00001343/2019-53]
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - CAPES
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq

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Abstract

Octovespin may be a potential drug for the treatment of Alzheimer's disease (AD) as it can prevent A beta aggregation and alleviate memory deficits.

Approximately 46.8 million people have been diagnosed worldwide with dementia, of which the most common type is Alzheimer's disease (AD). Since the current AD treatment is incipient and limited, it is essential to develop new drugs to prevent AD. Considering that evolutionary pressure selected animal venom compounds that are very specific for a unique target, those can be a potential drug against AD. Octovespin was modified from occidentalin-1202, which is a peptide isolated from Polybia occidentalis wasp venom. In this context, this study evaluated the effect of treatment with octovespin against Amyloid-beta (A beta)-induced toxicity, which is postulated to be one of the main causes of AD, in both in vitro and in vivo tests. In vitro, octovespin was able to prevent A beta aggregation in a ThT assay. In vivo, octovespin (0.15 nmol/animal) reverses memory impairment that is due to A beta toxicity, in the Morris Water Maze and Novel Object Recognition Test. Our results suggested that octovespin is a potential drug for the treatment of AD, due to its ability to avoid A beta aggregation in vitro and to prevent A beta-induced memory deficit in mice.

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Aggregation Limiting Cell-Penetrating Peptides Derived from Protein Signal Sequences

Ly Porosk, Heleri Heike Hark, Renata Naporano Bicev, Ilja Gaidutsik, Jekaterina Nebogatova, Eger-Jasper Armolik, Piret Arukuusk, Emerson Rodrigo da Silva, Ulo Langel

Summary: Alzheimer's disease (AD) is a common neurodegenerative disease that causes dementia, and its pathophysiological dynamics are driven by genetics with high heterogeneity in biological alterations and causes. The disease is characterized by the progression of aggregated amyloid-beta (A beta) or Tau neurofibrillary tangles. Current treatments for AD are not efficient, but recent breakthroughs have led to the discovery of potential therapeutic targets such as reducing brain inflammation and limiting A beta aggregation. This study demonstrates the successful use of A beta interacting protein sequences, particularly derived from Transthyretin, to reduce or target amyloid aggregation, and also predicts anti-inflammatory properties.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)