Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure-function relation to therapeutic inhibition.
Nutr Metab Cardiovasc Dis
; 21(11): 835-43, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21943799
ABSTRACT
AIMS:
This short review aims at summarizing the current information on Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) structure and function focusing also on the therapeutic possibilities based on the inhibition of this protein. DATASYNTHESIS:
PCSK9 has been recently discovered as the third gene involved in autosomal dominant hypercholesterolemia. PCSK9 binds and favors degradation of the low-density lipoprotein receptor (LDLR) and thereby modulates the plasma levels of LDL-cholesterol (LDL-C). Some of the natural occurring PCSK9 mutations increase the protein function (gain of function) and cause hypercholesterolemia, whereas loss of function mutations associate with hypocholesterolemia. Since the loss of a functional PCSK9 in humans is not associated with apparent deleterious effects, this protease is an attractive target for the development of lowering plasma LDL-C agents, either alone or in combination with statins.CONCLUSION:
Inhibition of PCSK9 is emerging as a novel strategy for the treatment of hypercholesterolemia and data obtained from pre-clinical studies show that use of monoclonal antibodies, antisense oligonucleotides and short interfering RNA are effective in reducing LDL-C, clinical studies, accompanied by a better understanding of PCSK9 biology, are now necessary to address whether these new compounds will have a future in clinical practice.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
/
Inibidores de Serina Proteinase
/
Hipercolesterolemia
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nutr Metab Cardiovasc Dis
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
CIENCIAS DA NUTRICAO
/
METABOLISMO
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Itália