Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a crucial role in lipid metabolism, particularly due to its function in low-density lipoprotein receptor degradation. Gain-of-function genetic mutations of PCSK9 result in autosomal dominant familial hypercholesterolemia, characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and clinical signs of early atherosclerosis. In recent years, PCSK9 has become an important therapeutic target for cholesterol-lowering therapy. Particularly, its inhibition with monoclonal antibodies has shown excellent efficacy in decreasing LDL-C and reducing cardiovascular events. However, PCSK9, first identified in the brain, seems to be a ubiquitous protein with different tissue-specific functions also independent of cholesterol metabolism. Accordingly, it appears to be involved in the immune response, haemostasis, glucose metabolism, neuronal survival, and several other biological functions. This review provides a comprehensive overview of the genetics, biochemical structure, expression, and function of PCSK9 and discusses the potential implications of its long-term pharmacological inhibition.
Scheda prodotto non validato
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo
Titolo: | Beyond cholesterol metabolism: The pleiotropic effects of proprotein convertase subtilisin/kexin type 9 (PCSK9). Genetics, mutations, expression, and perspective for long-term inhibition |
Autori: | |
Data di pubblicazione: | 2020 |
Rivista: | |
Abstract: | Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a crucial role in lipid metabolism, par...ticularly due to its function in low-density lipoprotein receptor degradation. Gain-of-function genetic mutations of PCSK9 result in autosomal dominant familial hypercholesterolemia, characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and clinical signs of early atherosclerosis. In recent years, PCSK9 has become an important therapeutic target for cholesterol-lowering therapy. Particularly, its inhibition with monoclonal antibodies has shown excellent efficacy in decreasing LDL-C and reducing cardiovascular events. However, PCSK9, first identified in the brain, seems to be a ubiquitous protein with different tissue-specific functions also independent of cholesterol metabolism. Accordingly, it appears to be involved in the immune response, haemostasis, glucose metabolism, neuronal survival, and several other biological functions. This review provides a comprehensive overview of the genetics, biochemical structure, expression, and function of PCSK9 and discusses the potential implications of its long-term pharmacological inhibition. |
Handle: | http://hdl.handle.net/11391/1462892 |
Appare nelle tipologie: | 1.1 Articolo in rivista |