An Engineered Variant of the B1 Domain of Protein G Suppresses the Aggregation and Toxicity of Intra- and Extracellular Aβ42
| Autor: | Ofek Oren, Bar Dagan, Ran Taube, Victor Banerjee, Stanislav Engel, Niv Papo |
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| Rok vydání: | 2018 |
| Předmět: |
Intracellular Fluid
Programmed cell death Saccharomyces cerevisiae Proteins Physiology Cognitive Neuroscience Peptide Protein aggregation Biochemistry Protein Aggregates 03 medical and health sciences 0302 clinical medicine Protein Domains Cell Line Tumor medicine Extracellular Humans Viability assay 030304 developmental biology chemistry.chemical_classification 0303 health sciences Amyloid beta-Peptides biology Neurodegeneration Extracellular Fluid Cell Biology General Medicine medicine.disease Peptide Fragments In vitro 3. Good health Cell biology chemistry biology.protein Protein G Genetic Engineering 030217 neurology & neurosurgery |
| Zdroj: | ACS Chemical Neuroscience. 10:1488-1496 |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.8b00491 |
| Popis: | Intra- and extraneuronal deposition of amyloid β (Aβ) peptides have been linked to Alzheimer's disease (AD). While both intra- and extraneuronal Aβ deposits affect neuronal cell viability, the molecular mechanism by which these Aβ structures, especially when intraneuronal, do so is still not entirely understood. This makes the development of inhibitors challenging. To prevent the formation of toxic Aβ structural assemblies so as to prevent neuronal cell death associated with AD, we used a combination of computational and combinatorial-directed evolution approaches to develop a variant of the HTB1 protein (HTB1M2). HTB1M2 inhibits in vitro self-assembly of Aβ42 peptide and shifts the Aβ42 aggregation pathway to the formation of oligomers that are nontoxic to neuroblastoma SH-SY5Y cells overexpressing or treated with Aβ42 peptide. This makes HTB1M2 a potential therapeutic lead in the development of AD-targeted drugs and a tool for elucidating conformational changes in the Aβ42 peptide. |
| Databáze: | OpenAIRE |
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