Zhang, X.; Yang, Y.; Hu, G.; Liu, R.; Zhou, N.; Song, X.; Basu, S.C.; Jing, M.; Hou, Q. Landscape of Intrinsically Disordered Proteins in Mental Disorder Diseases. Preprints2024, 2024020573. https://doi.org/10.20944/preprints202402.0573.v1
APA Style
Zhang, X., Yang, Y., Hu, G., Liu, R., Zhou, N., Song, X., Basu, S.C., Jing, M., & Hou, Q. (2024). Landscape of Intrinsically Disordered Proteins in Mental Disorder Diseases. Preprints. https://doi.org/10.20944/preprints202402.0573.v1
Chicago/Turabian Style
Zhang, X., Ming Jing and Qingzhen Hou. 2024 "Landscape of Intrinsically Disordered Proteins in Mental Disorder Diseases" Preprints. https://doi.org/10.20944/preprints202402.0573.v1
Abstract
Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking.
Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.
Keywords
mental disorder; intrinsically disordered protein; neural signaling; Neurological development
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
