Science & Technology, Canada (Commonwealth Union) – The nature of proteins often plays a key role in determining and identifying specific properties of diseases. Researchers in recent years have taken a particular interest in the role of specific proteins in diseases and its relation to the proteins necessary for the normal functions within cells.
A recent study has finally noted the molecular mechanism in which a vital protein regulates low density lipoproteins (LDL) cholesterol.
This is significant in gaining knowledge on the mechanisms playing a role in cardiovascular disease and some cancers, a research team has had significant success in a world 1st where they have discovered the molecular mechanism where the protein PCSK9 degrades the receptor of LDLs, which are the richest cholesterol particles within the bloodstream.
The finding was made by Professor Nabil G. Seidah, director of the biochemical neuroendocrinology research unit at the Montreal Clinical Research Institute and a medical professor at the University of Montreal, which was published in Molecular Metabolism.
The study was conducted jointly with Carole Fruchart Gaillard and colleagues at the Université de Paris-Saclay, Department of Drugs and Technologies for Health, together with scientists in the pharmacy department of the University of Pisa, in Italy.
HDL (high-density lipoprotein) which is referred to as the good cholesterol often plays a key role in eliminating the LDL levels in the blood.
LDLs, can build up in the blood and lead to heart conditions such as atherosclerosis. The level of LDL and the cholesterol linked to (LDLc), is directly modulated by LDL receptors (LDLR) being able to gather LDL from the bloodstream and internalize it, primarily within the cells of the liver. The surface LDLR drives LDL into the cell which traps it, and the LDLR goes back to the surface to be captured again.
The study further indicated that a majority of incidents with familial hypercholesterolemia are associated with LDLR dysfunction. But rarer cases have been associated with the PCSK9 protein, which the laboratory of Professor Seidah discovered in 2003. PCSK9 is also found in the bloodstream where it is linked with LDLR, enhancing its degradation by liver cells, and blocking it from re-emerging to the surface to capture LDL. Certain hypercholesterolemic patients have a “super PCSK9” promoting the degradation of the LDLR.
The effective treatments of recent times have been available to patients that block the function which are known as a monoclonal antibody or will lower the level of PCSK9 in the bloodstream, leading to bigger amounts of LDLR that ensure the lowering in LDLc of over 60% when contrasted to conventional statins.
The research of Professor Seidah and his team have revealed to the public the misunderstood mechanism on prior occasions by which PCSK9 pulls the LDLR towards the lysosomes, where cells break down the PCSK9-LDLR complex.
Professor Seidah and his team performed structural analyses from their lab that demonstrated the creation of a complex of 3 PCSK9 partner proteins, that included the LDLR, CAP1 and HLA-C.
A crucial protein within the immunity, HLA-C was noted to have a significant part as it directs the entire complex to the lysosomes. HLA-C makes way for the recognition of the “self”, and also enhances the anti-tumor activity of T lymphocytes.
PCSK9, plays the role of assisting in defending against the growth of tumours and associated metastasis by elevating the amount of HLA-C on the cell surface.
The researchers hope to eventually have inhibitors that can be produced that will block the interaction of PCSK9 and HLA-C and prevent the functioning of PCSK9 on LDLR and HLA-C.
This significant finding can then be utilized in the clinical practice to treat cardiovascular pathologies and also various types of cancer and metastases in patients.
