Aggregation Limiting Cell-Penetrating Peptides Derived from Protein Signal Sequences

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 5, p. 20-pg., 2023-03-01.

Resumo

Alzheimer's disease (AD) is the most common neurodegenerative disease (ND) and the leading cause of dementia. It is characterized by non-linear, genetic-driven pathophysiological dynamics with high heterogeneity in the biological alterations and the causes of the disease. One of the hallmarks of the AD is the progression of plaques of aggregated amyloid-beta (A beta) or neurofibrillary tangles of Tau. Currently there is no efficient treatment for the AD. Nevertheless, several breakthroughs in revealing the mechanisms behind progression of the AD have led to the discovery of possible therapeutic targets. Some of these include the reduction in inflammation in the brain, and, although highly debated, limiting of the aggregation of the A beta. In this work we show that similarly to the Neural cell adhesion molecule 1 (NCAM1) signal sequence, other A beta interacting protein sequences, especially derived from Transthyretin, can be used successfully to reduce or target the amyloid aggregation/aggregates in vitro. The modified signal peptides with cell-penetrating properties reduce the A beta aggregation and are predicted to have anti-inflammatory properties. Furthermore, we show that by expressing the A beta-EGFP fusion protein, we can efficiently assess the potential for reduction in aggregation, and the CPP properties of peptides in mammalian cells. (AU)

• Processo FAPESP: 22/03056-6 - Caracterização ultraestrutural de nanoscaffolds bioativos
• Beneficiário: Emerson Rodrigo da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Projeto Inicial