Research Article Details
| Article ID: | A10155 |
| PMID: | 31465774 |
| Source: | Biochem Pharmacol |
| Title: | Functions of aryl hydrocarbon receptor (AHR) and CD38 in NAD metabolism and nonalcoholic steatohepatitis (NASH). |
| Abstract: | Aryl hydrocarbon receptor (AHR), identified in studies of dioxin toxicity, has been characterized as ligand-activated transcription factor involved in diverse functions including microbial defense, cell proliferation, immunity and NAD metabolism. AHR targets of the latter function are PARPs/ARTs and CD38 that are regulating glucose and lipid metabolism via NAD-dependent sirtuins. Deregulation of these pathways may facilitate obesity and age-dependent pathologies. The present commentary is focused on AHR and CD38 signaling in liver. CD38 is functioning as ectoNADase and Ca2+ mobilizing enzyme in endoplasmic reticulum and endolysosomal membranes. Deregulation of TCDD-activated AHR and CD38 may facilitate hepatic steatosis and inflammation. However, these proteins are also involved in protection against inflammation and CD38-mediated age-related decreased NAD levels that may be responsible for neurodegeneration. Further knowledge about the complexity of these pathways is needed to avoid pathologies. Therapeutic modulation of AHR and CD38 remains a challenging task. |
| DOI: | 10.1016/j.bcp.2019.08.022 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D240 | Nicotinamide | Chemical drug | DB02701 | PARP inhibitor | Metabolic disorder drug | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D055 | Calcium | Chemical drug | DB01373 | CAST; COMP; CP; BMP4; MGP | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |