Proteostasis Regulation in the Endoplasmic Reticulum: An Emerging Theme in the Molecular Pathology and Therapeutic Management of Familial Hypercholesterolemia.

ABSTRACT: Familial hypercholesterolemia (FH) is an autosomal genetic disease characterized by high serum low-density lipoprotein (LDL) content leading to premature coronary artery disease. The main genetic and molecular causes of FH are mutations in low-density lipoprotein receptor gene (LDLR) resulting in the non-clearance of LDL from the blood by hepatocytes and consequently the formation of plaques. LDLR is synthesized and glycosylated in the endoplasmic reticulum (ER) and then transported to the plasma membrane via Golgi. It is estimated that more than 50% of reported FH-causing mutations in LDLR result in misfolded proteins that are transport-defective and hence retained in ER. ER accumulation of misfolded proteins causes ER-stress and activates unfolded protein response (UPR). UPR aids

SUBMITTER: Oommen D 

PROVIDER: S-EPMC7538668 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature