The New Discovery of Inhibitors for the Treatment of Alzheimer's Disease

The Drug Discovery Lab, under the direction of Professor Varghese John, announced in the May 14, 2020 edition of UCLA Health news the publication in ACS Chemical Biology of their "... Discovery of a novel class of compounds that function as dual inhibitors of the enzymes neutral sphingomyelinase-2 (nSMase2) and acetylcholinesterase (AChE). Inhibition of these enzymes provides a unique strategy to suppress the propagation of tau pathology in the treatment of Alzheimer's disease (AD)." In the report, they describe the key structure-activity relationship elements that affect relative nSMase2 and/or AChE inhibitor effects and potency, as well as the identification of two compound analogs that suppress the release of tau-bearing exosomes in vitro and in vivo. Dr. John stated “Identification of these novel dual nSMase2/AChE inhibitors represents a new therapeutic approach to AD and has the potential to lead to the development of truly disease-modifying therapeutics." Read more in ACS Chemical Biology.

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