An experimental drug restored the ability of liver cells in old rats to filter blood, opening a new path to treating Alzheimer's disease and atherosclerosis, the website infohub.kz reports.
Scientists at the Keck School of Medicine of the University of Southern California (USC) have made a discovery that could change approaches to fighting Alzheimer's disease and cardiovascular pathologies. In laboratory experiments, the researchers found that restoring the function of aging liver cells clears the bloodstream of dangerous substances that damage distant organs, including the brain. The results of the study were published in the scientific journal Journal of Biological Chemistry.
The focus of the specialists was on liver sinusoidal endothelial cells (LSEC). They line the capillaries of the organ and have microscopic pores through which large molecules reach hepatocytes for neutralization. With age, these openings narrow or disappear entirely, causing toxic compounds to accumulate in the blood. Among them is beta-amyloid, the key protein that forms plaques in Alzheimer's disease. To reverse the degradation of the filters, elderly rats were given the drug cinaciguat for two weeks.
The therapy fully restored the structure of the LSEC cells and opened their pores, halving the concentration of beta-amyloid — down to the levels of young specimens. An unexpected effect was a drop in the level of low-density lipoprotein (LDL), known as bad cholesterol. It turned out that the drug activates the enzyme soluble guanylate cyclase, prompting the endothelium to produce the growth factor HB-EGF. This signal causes hepatocytes to take up LDL and the toxic protein from the bloodstream more actively.
The scientists emphasize the particular importance of the liver-based approach to treating neurodegeneration. Clinical trials of Alzheimer's drugs aimed directly at brain tissue fail in 98% of cases because of the blood-brain barrier, which impedes the delivery of molecules. Delivering drugs to the liver is technically simpler and more promising. The authors must now test whether clearing the blood will reduce plaque formation in the brain itself in clinical trials.