Glycogen synthase kinase 3: an emerging therapeutic target

被引:378
作者
Eldar-Finkelman, H [1 ]
机构
[1] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel
关键词
D O I
10.1016/S1471-4914(01)02266-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that has recently emerged as a key target in drug discovery. It has been implicated in multiple cellular processes and linked with the pathogenesis of several diseases. GSK-3 inhibitors might prove useful as therapeutic compounds in the treatment of conditions associated with elevated levels of enzyme activity, such as type 2 diabetes and Alzheimer's disease. The pro-apoptotic feature of GSK-3 activity suggests a potential role for its inhibitors in protection against neuronal cell death, and in the treatment of traumatic head injury and stroke. Finally, selective inhibitors of GSK-3 could mimic the action of mood stabilizers such as lithium and valproic acid and be used in the treatment of bipolar mood disorders.
引用
收藏
页码:126 / 132
页数:7
相关论文
共 61 条
[11]   Crystal structure of glycogen synthase kinase 3β:: Structural basis for phosphate-primed substrate specificity and autoinhibition [J].
Dajani, R ;
Fraser, E ;
Roe, SM ;
Young, N ;
Good, V ;
Dale, TC ;
Pearl, LH .
CELL, 2001, 105 (06) :721-732
[12]   Anti-mitotic properties of indirubin-3'-monoxime, a CDK/GSK-3 inhibitor: induction of endoreplication following prophase arrest [J].
Damiens, E ;
Baratte, B ;
Marie, D ;
Eisenbrand, G ;
Meijer, L .
ONCOGENE, 2001, 20 (29) :3786-3797
[13]   THE MOLECULAR MECHANISM BY WHICH INSULIN STIMUALTES GLYCOGEN-SYNTHESIS IN MAMMALIAN SKELETAL-MUSCLE [J].
DENT, P ;
LAVOINNE, A ;
NAKIELNY, S ;
CAUDWELL, FB ;
WATT, P ;
COHEN, P .
NATURE, 1990, 348 (6299) :302-308
[14]   Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice [J].
Eldar-Finkelman, H ;
Schreyer, SA ;
Shinohara, MM ;
LeBoeuf, RC ;
Krebs, EG .
DIABETES, 1999, 48 (08) :1662-1666
[15]   Expression and characterization of glycogen synthase kinase-3 mutants and their effect on glycogen synthase activity in intact cells [J].
EldarFinkelman, H ;
Argast, GM ;
Foord, O ;
Fischer, EH ;
Krebs, EG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (19) :10228-10233
[16]   Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action [J].
EldarFinkelman, H ;
Krebs, EG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (18) :9660-9664
[17]  
FEA KD, 1998, BIOCHEMISTRY-US, V36, P12939
[18]   A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation [J].
Frame, S ;
Cohen, P ;
Biondi, RM .
MOLECULAR CELL, 2001, 7 (06) :1321-1327
[19]   GSK3 takes centre stage more than 20 years after its discovery [J].
Frame, S ;
Cohen, P .
BIOCHEMICAL JOURNAL, 2001, 359 (01) :1-16
[20]   The pathogenic L392V mutation of presenilin 1 decreases the affinity to glycogen synthase kinase-3β [J].
Gantier, R ;
Gilbert, D ;
Dumanchin, C ;
Campion, D ;
Davoust, D ;
Toma, F ;
Frébourg, T .
NEUROSCIENCE LETTERS, 2000, 283 (03) :217-220