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Details on Person Low-density lipoprotein (LDL) receptors expressed on hepatoc...
| Class:Id | Summation:9733387 |
|---|---|
| _displayName | Low-density lipoprotein (LDL) receptors expressed on hepatoc... |
| _timestamp | 2021-06-04 13:17:13 |
| created | [InstanceEdit:9733402] Jassal, Bijay, 2021-06-04 |
| literatureReference | [LiteratureReference:8855117] The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2 [LiteratureReference:9733430] Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9 [LiteratureReference:9733429] A Highly Durable RNAi Therapeutic Inhibitor of PCSK9 [LiteratureReference:9733370] Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates [LiteratureReference:9733448] Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia |
| modified | [InstanceEdit:9733441] Jassal, Bijay, 2021-06-04 [InstanceEdit:9733442] Jassal, Bijay, 2021-06-04 [InstanceEdit:9733444] Jassal, Bijay, 2021-06-04 [InstanceEdit:9733453] Jassal, Bijay, 2021-06-04 [InstanceEdit:9733454] Jassal, Bijay, 2021-06-04 [InstanceEdit:9733455] Jassal, Bijay, 2021-06-04 |
| text | Low-density lipoprotein (LDL) receptors expressed on hepatocytes mediate the removal of circulating LDL-cholesterol (LDL-C) from plasma via a receptor-mediated endocytic process. High circulating levels of LDL-C contributes to hypercholesterolemia, which is a known risk factor for cardiovascular disease. The PCSK9 gene produces proprotein convertase subtilisin/kexin type 9 (neural apoptosis-regulated convertase 1, NARC1), an important regulator of plasma cholesterol homeostasis (Seidah et al. 2003). It binds to low-density lipoprotein receptor (LDLR) family members and promotes their degradation in intracellular acidic compartments (Poirer et al. 2008). This results in lower numbers of LDLRs on the surface of hepatocytes and as a consequence, circulating plasma levels of LDL-C are elevated. Inclisiran is a long-acting, synthetic small interfering RNA (siRNA) directed against PCSK9. It binds to PCSK9 messenger RNA, preventing the translation of PCSK9 and thereby decreasing PCSK9 protein concentrations (Fitzgerald et al. 2017, German & Shapiro 2020). It does this by binding to the RNA-induced silencing complex (RISC), a template that recognizes the target complementary mRNA, activates RNAse, and cleaves the target mRNA. Less PCSK9 protein allows more LDLRs to be recycled to the hepatic membrane for the uptake of circulating LDL-C, thereby lowering plasma LDL-C levels. Inclisiran is administered by subcutaneous injection and is indicated for the treatment of primary hypercholesterolemia (familial and non-familial) or mixed dyslipidemia in adults (Frank-Kamenetsky et al. 2008, Kosmas et al. 2018). For simplification, the processes of transcription and translation are not described in this reaction. |
| (summation) | [BlackBoxEvent:9733406] PCSK9 gene expression [Homo sapiens] |
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No pathways have been reviewed or authored by Low-density lipoprotein (LDL) receptors expressed on hepatoc... (9733387)
