Modulation of Disordered Proteins with a Focus on Neurodegenerative Diseases and Other Pathologies
AbstractIntrinsically disordered proteins (IDPs) do not have rigid 3D structures, showing changes in their folding depending on the environment or ligands. Intrinsically disordered proteins are widely spread in eukaryotic genomes, and these proteins participate in many cell regulatory metabolism processes. Some IDPs, when aberrantly folded, can be the cause of some diseases such as Alzheimer′s, Parkinson′s, and prionic, among others. In these diseases, there are modifications in parts of the protein or in its entirety. A common conformational variation of these IDPs is misfolding and aggregation, forming, for instance, neurotoxic amyloid plaques. In this review, we discuss some IDPs that are involved in neurodegenerative diseases (such as beta amyloid, alpha synuclein, tau, and the “IDP-like” PrP), cancer (p53, c-Myc), and diabetes (amylin), focusing on the structural changes of these IDPs that are linked to such pathologies. We also present the IDP modulation mechanisms that can be explored in new strategies for drug design. Lastly, we show some candidate drugs that can be used in the future for the treatment of diseases caused by misfolded IDPs, considering that cancer therapy has more advanced research in comparison to other diseases, while also discussing recent and future developments in this area of research. Therefore, we aim to provide support to the study of IDPs and their modulation mechanisms as promising approaches to combat such severe diseases. View Full-Text
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Martinelli, A.H.S.; Lopes, F.C.; John, E.B.O.; Carlini, C.R.; Ligabue-Braun, R. Modulation of Disordered Proteins with a Focus on Neurodegenerative Diseases and Other Pathologies. Int. J. Mol. Sci. 2019, 20, 1322.
Martinelli AHS, Lopes FC, John EBO, Carlini CR, Ligabue-Braun R. Modulation of Disordered Proteins with a Focus on Neurodegenerative Diseases and Other Pathologies. International Journal of Molecular Sciences. 2019; 20(6):1322.Chicago/Turabian Style
Martinelli, Anne H.S.; Lopes, Fernanda C.; John, Elisa B.O.; Carlini, Célia R.; Ligabue-Braun, Rodrigo. 2019. "Modulation of Disordered Proteins with a Focus on Neurodegenerative Diseases and Other Pathologies." Int. J. Mol. Sci. 20, no. 6: 1322.
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