The Sherpa hypothesis: Phenotype-Preserving Disordered Proteins stabilize the phenotypes of neurons and oligodendrocytes

Bibliographic Details
Title: The Sherpa hypothesis: Phenotype-Preserving Disordered Proteins stabilize the phenotypes of neurons and oligodendrocytes
Authors: Vic Norris, Judit Oláh, Sergey N. Krylov, Vladimir N. Uversky, Judit Ovádi
Source: npj Systems Biology and Applications, Vol 9, Iss 1, Pp 1-11 (2023)
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Biology (General)
Subject Terms: Biology (General), QH301-705.5
More Details: Abstract Intrinsically disordered proteins (IDPs), which can interact with many partner proteins, are central to many physiological functions and to various pathologies that include neurodegeneration. Here, we introduce the Sherpa hypothesis, according to which a subset of stable IDPs that we term Phenotype-Preserving Disordered Proteins (PPDP) play a central role in protecting cell phenotypes from perturbations. To illustrate and test this hypothesis, we computer-simulate some salient features of how cells evolve and differentiate in the presence of either a single PPDP or two incompatible PPDPs. We relate this virtual experiment to the pathological interactions between two PPDPs, α-synuclein and Tubulin Polymerization Promoting Protein/p25, in neurodegenerative disorders. Finally, we discuss the implications of the Sherpa hypothesis for aptamer-based therapies of such disorders.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2056-7189
Relation: https://doaj.org/toc/2056-7189
DOI: 10.1038/s41540-023-00291-8
Access URL: https://doaj.org/article/7dd45f5817ee46808b99c8c0e59e18a0
Accession Number: edsdoj.7dd45f5817ee46808b99c8c0e59e18a0
Database: Directory of Open Access Journals
More Details
ISSN:20567189
DOI:10.1038/s41540-023-00291-8
Published in:npj Systems Biology and Applications
Language:English