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Study of NAD-interacting proteins highlights the extent of NAD regulatory roles in the cell and its potential as a therapeutic target.
Duarte-Pereira, Sara; Matos, Sérgio; Oliveira, José Luís; Silva, Raquel M.
Affiliation
  • Duarte-Pereira S; IEETA/DETI, University of Aveiro, Aveiro, Portugal.
  • Matos S; Department of Medical Sciences, iBiMED - Institute of Biomedicine, University of Aveiro, Aveiro, Portugal.
  • Oliveira JL; IEETA/DETI, University of Aveiro, Aveiro, Portugal.
  • Silva RM; LASI - Intelligent Systems Associate Laboratory, Guimarães, Portugal.
J Integr Bioinform ; 20(2)2023 Jun 01.
Article in En | MEDLINE | ID: mdl-36880517
Nicotinamide adenine dinucleotide (NAD) levels are essential for the normal physiology of the cell and are strictly regulated to prevent pathological conditions. NAD functions as a coenzyme in redox reactions, as a substrate of regulatory proteins, and as a mediator of protein-protein interactions. The main objectives of this study were to identify the NAD-binding and NAD-interacting proteins, and to uncover novel proteins and functions that could be regulated by this metabolite. It was considered if cancer-associated proteins were potential therapeutic targets. Using multiple experimental databases, we defined datasets of proteins that directly interact with NAD - the NAD-binding proteins (NADBPs) dataset - and of proteins that interact with NADBPs - the NAD-protein-protein interactions (NAD-PPIs) dataset. Pathway enrichment analysis revealed that NADBPs participate in several metabolic pathways, while NAD-PPIs are mostly involved in signalling pathways. These include disease-related pathways, namely, three major neurodegenerative disorders: Alzheimer's disease, Huntington's disease, and Parkinson's disease. Then, the complete human proteome was further analysed to select potential NADBPs. TRPC3 and isoforms of diacylglycerol (DAG) kinases, which are involved in calcium signalling, were identified as new NADBPs. Potential therapeutic targets that interact with NAD were identified, that have regulatory and signalling functions in cancer and neurodegenerative diseases.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neurodegenerative Diseases / Neoplasms Limits: Humans Language: En Journal: J Integr Bioinform Journal subject: INFORMATICA MEDICA Year: 2023 Document type: Article Affiliation country: Portugal Country of publication: Germany

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neurodegenerative Diseases / Neoplasms Limits: Humans Language: En Journal: J Integr Bioinform Journal subject: INFORMATICA MEDICA Year: 2023 Document type: Article Affiliation country: Portugal Country of publication: Germany