THE COGNITION-ENHANCING DRUG TENILSETAM IS AN INHIBITOR OF PROTEIN CROSS-LINKING BY ADVANCED GLYCOSYLATION

被引:70
作者
MUNCH, G
TANELI, Y
SCHRAVEN, E
SCHINDLER, U
SCHINZEL, R
PALM, D
RIEDERER, P
机构
[1] UNIV WURZBURG,NERVENKLIN,DEPT PSYCHIAT,D-97080 WURZBURG,GERMANY
[2] CASSELLA AG,CNS PHARMACOL,FRANKFURT,GERMANY
[3] UNIV WURZBURG,THEODOR BOVERI INST,WURZBURG,GERMANY
关键词
MAILLARD REACTION; ADVANCED GLYCOSYLATION; TENILSETAM; DEMENTIA OF ALZHEIMER TYPE; AMYLOID;
D O I
10.1007/BF02260940
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 ((R)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.
引用
收藏
页码:193 / 208
页数:16
相关论文
共 54 条
[1]   THE NON-ENZYMIC GLYCOSYLATION OF BOVINE LENS PROTEINS BY GLUCOSAMINE AND ITS INHIBITION BY ASPIRIN, IBUPROFEN AND GLUTATHIONE [J].
AJIBOYE, R ;
HARDING, JJ .
EXPERIMENTAL EYE RESEARCH, 1989, 49 (01) :31-41
[2]  
BEYREUTHER K, 1993, DEMENTIAS NEUROCHEMI, P103
[3]  
BLAKYTNY R, 1992, EXP EYE RES, V54, P509
[4]  
BRION JP, 1990, ALZHEIMERS DISEASE E, P131
[5]   TRAPPED IMMUNOGLOBULINS ON PERIPHERAL-NERVE MYELIN FROM PATIENTS WITH DIABETES-MELLITUS [J].
BROWNLEE, M ;
VLASSARA, H ;
CERAMI, A .
DIABETES, 1986, 35 (09) :999-1003
[6]   GLYCOSYLATION PRODUCTS AS TOXIC MEDIATORS OF DIABETIC COMPLICATIONS [J].
BROWNLEE, M .
ANNUAL REVIEW OF MEDICINE, 1991, 42 :159-166
[7]  
BUCCALA R, 1992, ADV PHARMACOL, V23, P1
[8]  
CERAMI A, 1988, DIABETES CARE, V11, P73
[9]   INVITRO GLYCATION AND ACETYLATION (BY ASPIRIN) OF RAT CRYSTALLINS [J].
CHERIAN, M ;
ABRAHAM, EC .
LIFE SCIENCES, 1993, 52 (21) :1699-1707
[10]   GLYCATION OF RAT SCIATIC-NERVE TUBULIN IN EXPERIMENTAL DIABETES-MELLITUS [J].
CULLUM, NA ;
MAHON, J ;
STRINGER, K ;
MCLEAN, WG .
DIABETOLOGIA, 1991, 34 (06) :387-389