Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibition
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. Data synthesis: PCSK9 has been recently discovered as the third...
| Main Authors: | , , , , |
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| Format: | Journal Article |
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Elsevier
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/55419 |
| _version_ | 1848759616164331520 |
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| author | Tibolla, G. Norata, Giuseppe Artali, R. Meneghetti, F. Catapano, A. |
| author_facet | Tibolla, G. Norata, Giuseppe Artali, R. Meneghetti, F. Catapano, A. |
| author_sort | Tibolla, G. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. Data synthesis: 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. © 2011 Elsevier B.V. |
| first_indexed | 2025-11-14T10:02:43Z |
| format | Journal Article |
| id | curtin-20.500.11937-55419 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:02:43Z |
| publishDate | 2011 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-554192017-09-13T16:11:12Z Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibition Tibolla, G. Norata, Giuseppe Artali, R. Meneghetti, F. Catapano, A. 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. Data synthesis: 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. © 2011 Elsevier B.V. 2011 Journal Article http://hdl.handle.net/20.500.11937/55419 10.1016/j.numecd.2011.06.002 Elsevier restricted |
| spellingShingle | Tibolla, G. Norata, Giuseppe Artali, R. Meneghetti, F. Catapano, A. Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibition |
| title | Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibition |
| title_full | Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibition |
| title_fullStr | Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibition |
| title_full_unstemmed | Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibition |
| title_short | Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibition |
| title_sort | proprotein convertase subtilisin/kexin type 9 (pcsk9): from structure-function relation to therapeutic inhibition |
| url | http://hdl.handle.net/20.500.11937/55419 |