A novel insight into neurological disorders through HDAC6 protein–protein interactions

• Published in: Scientific reports Vol. 14; no. 1; pp. 14666 - 14
• Main Authors: Bahram Sangani, Nasim, Koetsier, Jarno, Mélius, Jonathan, Kutmon, Martina, Ehrhart, Friederike, Evelo, Chris T., Curfs, Leopold M. G., Reutelingsperger, Chris P., Eijssen, Lars M. T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114/2406; 631/337; 631/378; Acetylation; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Amyotrophic lateral sclerosis; Autophagy; Central nervous system; Deacetylation; Histone deacetylase; Histone deacetylase 6 (HDAC6); Histone Deacetylase 6 - genetics; Histone Deacetylase 6 - metabolism; Humanities and Social Sciences; Humans; multidisciplinary; Nervous System Diseases - genetics; Nervous System Diseases - metabolism; Neurodegenerative diseases; Neurological diseases; Neurological disorders; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Pharmacodynamics; Phosphorylation; Protein interaction; Protein Interaction Maps; Proteins; Protein–protein interactions; Science; Science (multidisciplinary); Transcriptomics; Amyotrophic lateral sclerosis; Protein–protein interactions; Alzheimer’s disease; Histone deacetylase 6 (HDAC6); Parkinson’s disease; Central nervous system
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-65094-1

Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several neurological manifestations. However, the exact regulatory role of HDAC6 in the central nervous system (CNS) is still not fully understood. Hence, using a semi-automated literature screening technique, we systematically collected HDAC6-protein interactions that are experimentally validated and reported in the CNS. The resulting HDAC6 network encompassed 115 HDAC6-protein interactions divided over five subnetworks: (de)acetylation, phosphorylation, protein complexes, regulatory, and aggresome-autophagy subnetworks. In addition, 132 indirect interactions identified through HDAC6 inhibition were collected and categorized. Finally, to display the application of our HDAC6 network, we mapped transcriptomics data of Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis on the network and highlighted that in the case of Alzheimer’s disease, alterations predominantly affect the HDAC6 phosphorylation subnetwork, whereas differential expression within the deacetylation subnetwork is observed across all three neurological disorders. In conclusion, the HDAC6 network created in the present study is a novel and valuable resource for the understanding of the HDAC6 regulatory mechanisms, thereby providing a framework for the integration and interpretation of omics data from neurological disorders and pharmacodynamic assessments.