Statins Modulate Amyloid Plaque Production

Researchers have found that statins, drugs valued for their cholesterol-lowering properties, may help patients with Alzheimer's disease by reducing the activity of Rock1 (Rho-associated kinase beta), a serine/threonine kinase involved in intracellular signaling.


Statins reduce cholesterol by competitively inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme of the HMG-CoA reductase pathway, the body's metabolic pathway for the synthesis of cholesterol. Although statins inhibit endogenous cholesterol synthesis, their action goes further than that. By reducing intracellular cholesterol levels, liver cells upregulate expression of the low-density lipoprotein (LDL) receptor, leading to increased clearance of LDL from the bloodstream. Statins display other modes of action beyond lipid lowering in the prevention of atherosclerosis. These include improving endothelial function, modulating inflammatory responses, maintaining plaque stability, and preventing thrombus formation.

Investigators at Thomas Jefferson University (Philadelphia, PA, USA) conducted a study to determine which mode of action causes statins to have a moderating effect on Alzheimer's disease. They found that statins act on the Rho/ROCK enzymatic pathway. When this pathway is active, more toxic amyloid proteins are produced, while when the pathway is inhibited fewer toxic proteins are produced. These findings were published in the January 11, 2005, online edition of Public Library of Science Medicine.

"This reveals an unsuspected pathway linking statins and amyloid metabolism,” said senior author Dr. Sam Gandy, director of the Farber Institute for Neurosciences at Thomas Jefferson University. "This may help unravel statin action in Alzheimer's as well as point the way toward novel anti-amyloid drugs.”




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