Aggregation Limiting Cell-Penetrating Peptides Derived from Protein Signal Sequences
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Published:2023-02-21
Issue:5
Volume:24
Page:4277
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Porosk Ly1ORCID, Härk Heleri Heike1ORCID, Bicev Renata Naporano2, Gaidutšik Ilja1, Nebogatova Jekaterina1ORCID, Armolik Eger-Jasper1, Arukuusk Piret1, da Silva Emerson Rodrigo2ORCID, Langel Ülo13
Affiliation:
1. Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia 2. Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil 3. Department Biochemistry and Biophysics, Stockholm University, S.Arrheniusv. 16B, Room C472, 106 91 Stockholm, Sweden
Abstract
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-β (Aβ) 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 Aβ. In this work we show that similarly to the Neural cell adhesion molecule 1 (NCAM1) signal sequence, other Aβ 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 Aβ aggregation and are predicted to have anti-inflammatory properties. Furthermore, we show that by expressing the Aβ-EGFP fusion protein, we can efficiently assess the potential for reduction in aggregation, and the CPP properties of peptides in mammalian cells.
Funder
EU Swedish Research Council FAPESP CNPq AFM instruments
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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