Tag

Ctsa

All articles tagged with #ctsa

New Cholesterol-Lowering Pathway Uncovered, Points to CTSA-Targeted Therapy
health-and-medicine1 month ago

New Cholesterol-Lowering Pathway Uncovered, Points to CTSA-Targeted Therapy

Researchers identify a new pathway where high dietary cholesterol activates the Ral protein, reducing liver LDL receptors and hindering clearance of LDL cholesterol. Blocking the enzyme cathepsin A (CTSA) with a small-molecule inhibitor stabilized LDL receptors and dramatically lowered blood cholesterol in mouse models, suggesting a novel, statin-independent approach and a potential CTSA-targeted treatment that could move to clinical trials, leveraging an existing CTSA inhibitor with prior human safety data.

Cholesterol triggers a Ral-driven LDLR turnover pathway in the liver
science2 months ago

Cholesterol triggers a Ral-driven LDLR turnover pathway in the liver

A new study shows that high dietary cholesterol activates Ral GTPases in the liver via increased RAS activity, promoting LDL receptor (LDLR) endocytosis and lysosomal degradation through the RalBP1–REPS1 complex and the lysosomal protease CTSA, independently of PCSK9 or transcriptional control; LDLR levels fall and cholesterol clearance is impaired, with human genetic variants linking this pathway to cholesterol levels. Pharmacological inhibition of Ral or CTSA stabilizes LDLR and improves cholesterol clearance, pointing to a potential new therapy for hypercholesterolemia and cardiovascular disease.