The cognition-enhancing drug tenilsetam is an inhibitor of protein crosslinking by advanced glycosylation.
Non-enzymatic glycosylation of proteins, also called Maillard reaction, which occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation endproducts (AGEs). Tenilsetam (CAS 997: (+/-)-3-(2-thienyl)-2-piperazinone), a cognition-enhancing drug successfully used for treatment of patients suffering from Alzheimer's disease, when included in the Maillard reaction apparently inhibits protein crosslinking by AGEs in vitro. According to the mechanism proposed, Tenilsetam acts via covalent attachment to glycated proteins, thus blocking the reactive sites for further polymerisation reactions. A beneficial effect of Tenilsetam in Alzheimer's disease could come from the interference with AGE-derived crosslinking of amyloid plaques and a decreased inflammatory response by diminished activation of phagocytosing microglia.
Münch
G
G
Department of Psychiatry, University of Würzburg, Federal Republic of Germany.
Taneli
Y
Y
Schraven
E
E
Schindler
U
U
Schinzel
R
R
Palm
D
D
Riederer
P
P
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000502:physiology; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D017127:Glycation End Products, Advanced; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D010879:Piperazines; D011619:Psychotropic Drugs; D013876:Thiophenes; C059511:tenilsetam