Oral cambinol cure present potential for blocking progress of alzheimer’s disease

Alzheimer’s disease researchers have shown that the low molecular weight drug cambinol blocks the formation of exosomes that allow the scatter of insoluble, toxic tau entirety, characteristic neurodegenerative disorder. Tau proteins are components of the cytoskeleton of neurons, but in Alzheimer’s disease, tau proteins become abnormally amend and condense into insoluble from “neurofibrillary tangles” for that demolish these brain cells. Furthermore, dying cells encase tau aggregates in exosome lipid vesicles, which bud off and “seed” neighbouring tissues, expand the disease. During a screen of potential drug candidates capable of blocking the seeding of tau tangles, investigators at the University of California, Los Angeles (USA), identified the compound cambinol. Foregoing studies had shown that cambinol was a novel uncompetitive inhibitor of the enzyme nSMase2 (neutral sphingomyelinase 2). The enzyme nSMase2 had been found to be critically statutory for catalyzing the production of exosome vesicles.
The inhibitory activity of cambinol for nSMase2 was approximately 10-fold more potent than for its formerly known target, SIRT1/2 (silence information regulator 1 and 2). Cambinol decreased tumor necrosis factor-alpha or interleukin-1 beta-induced increases of ceramide and cell death in primary neurons. A preliminary study of cambinol structure and activity identified the main structural features required for nSMase2 inhibition.The investigators demonstrated that cambinol was an inhibitor of cell-to-cell tau propagation. Decreased nSMase2 catalytic activity was observed in the brains of mice given oral cambinol. In vivo testing in mice showed that cambinol could reduce the nSMase2 activity in the brain after oral administration.
Original link: https://www.biotechdaily.com/drug-discovery/articles/294773512/oral-cambinol-treatment-shows-potential-for-blocking-development-of-ad.html