Modulation of Disordered Proteins with a Focus on Neurodegenerative Diseases and Other Pathologies

International Journal of Molecular Sciences

FernandaC. Lopes¹  ElisaB. O. John²  CéliaR. Carlini²  AnneH. S. Martinelli³  Rodrigo Ligabue-Braun⁴ 

[1] Department of Biophysics, Biosciences Institute-IB, (UFRGS), Porto Alegre CEP 91501-970, RS, Brazil;Center for Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre CEP 91501-970, RS, Brazil;;Department of Molecular Biology and Biotechnology &Graduate Program in Cell and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre CEP 91501-970, RS, Brazil;

关键词: intrinsically disordered proteins (IDPs);    neurodegenerative diseases;    aggregation;    drugs;    drug discovery;   

DOI  :  10.3390/ijms20061322

来源: DOAJ

【 摘 要 】

Intrinsically 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.

【 授权许可】

Unknown