The discovery of PCSK9, its structure-function features, and it’s currently known and hypothesized new biological roles were discussed by researchers for a study. The main crucial function of PCSK9 inferred from human and animal research, as well as cellular and structural analysis, is its capacity to promote the sorting and transport of the cell surface LDL receptor (LDLR) to lysosomes. It implied that the PCSK9 catalytic domain binds to the LDLR’s EGF-A domain. It also necessitated the existence of the C-terminal Cys/His-rich domain, as well as its interaction with the secreted cytosolic cyclase associated protein 1 and maybe another membrane-bound “protein X.”
Recent research expanded the understanding of PCSK9’s biological functions, specifically its role in septic shock, vascular inflammation, viral infections (Dengue; SARS-CoV-2), and immune checkpoint modulation in cancer via the regulation of T-cell receptor and MHC-I cell surface levels, which govern the antitumoral activity of CD8+ T cells. Because PCSK9 inhibition may be beneficial in these processes, the availability of injectable safe PCSK9 inhibitors that lower LDLc by 50% to 60% over the impact of statins is extremely useful. Injectable PCSK9 monoclonal antibodies or small interfering RNA might be added to existing cancer/metastasis immunotherapies.
Reference:academic.oup.com/edrv/article/43/3/558/6385885
