Research Article Details
| Article ID: | A07922 |
| PMID: | 32308060 |
| Source: | Free Radic Res |
| Title: | Emerging connections between oxidative stress, defective proteolysis, and metabolic diseases. |
| Abstract: | The ubiquitin-proteasome system (UPS) and autophagy are two major intracellular proteolytic systems that are closely associated with each other. Because UPS and autophagy are involved in the clearance of oxidised and/or aggregated proteins, it would be logical to assume that alterations in proteolysis would accompany pathological conditions. Indeed, both systems are themselves susceptible to oxidative modification and therefore could be a prominent target of reactive oxygen species (ROS). Oxidative stress appears to be a common underlying factor in the development of and the pathogenesis of various metabolic diseases, including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). Recent studies, using obesity and hyperglycaemia model mice, reported that both UPS and autophagy systems are inhibited in these mice and that this inhibition is accompanied by lipid accumulation, insulin resistance, and tissue damage. However, the detailed molecular mechanisms that are responsible for regulating intracellular proteolysis in metabolic diseases are not well understood. In the current review, we discuss the correlation between oxidative stress, defective proteolysis, and metabolic diseases. An understanding of how ROS affects intracellular proteolysis may provide new perspectives on the development of and control of diseases. |
| DOI: | 10.1080/10715762.2020.1734588 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| 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 |