Understanding Glycogen Synthase Kinase-3: A Novel Avenue for Alzheimer's Disease

被引:7
|
作者
Sequeira, Ronnita C. [1 ]
Godad, Angel [1 ,2 ]
机构
[1] SVKMs Dr Bhanuben Nanavati Coll Pharm, Gate 1,Mithibai Coll Campus,Vaikunthlal Mehta Rd, Mumbai 400056, Maharashtra, India
[2] Inst Chem Technol, Dept Pharmaceut Sci & Technol, Mumbai, Maharashtra, India
关键词
GSK-3; beta; Alzheimer's Disease; Tau; Amyloid-beta; inhibitors; Synaptic plasticity; RABBIT SKELETAL-MUSCLE; AMYLOID-BETA; LITHIUM TREATMENT; PROTEIN-KINASE; TAU PHOSPHORYLATION; AXONAL-TRANSPORT; CELL-DEATH; IN-VITRO; SUBSTRATE-SPECIFICITY; TRANSGENIC MODEL;
D O I
10.1007/s12035-023-03839-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Alzheimer's Disease (AD) is the most prevalent form of age-related dementia. Even though a century has passed since the discovery of AD, the exact cause of the disease still remains unknown. As a result, this poses a major hindrance in developing effective therapies for treating AD. Glycogen synthase kinase-3 (GSK-3) is one of the kinases that has been investigated recently as a potential therapeutic target for the treatment of AD. It is also known as human tau protein kinase and is a proline-directed serine-threonine kinase. Since dysregulation of this kinase affects all the major characteristic features of the disease, such as tau phosphorylation, amyloid formation, memory, and synaptic function, it is thought to be a major player in the pathogenesis of AD. In this review, we present the most recent information on the role of this kinase in the onset and progression of AD, as well as significant findings that identify GSK-3 as one of the most important targets for AD therapy. We further discuss the potential of treating AD by targeting GSK-3 and give an overview of the ongoing studies aimed at developing GSK-3 inhibitors in preclinical and clinical investigations.
引用
收藏
页码:4203 / 4221
页数:19
相关论文
共 50 条
  • [41] The peripheral messenger RNA expression of glycogen synthase kinase-3β genes in Alzheimer's disease patients: a preliminary study
    Sheng, Jian-Hua
    Ng, Tze-Pin
    Li, Chun-Bo
    Lu, Guang-Hua
    He, Wei
    Qian, Yi-Ping
    Wang, Jing-Hua
    Yu, Shun-Ying
    PSYCHOGERIATRICS, 2012, 12 (04) : 248 - 254
  • [42] Neuroprotection and Mechanism of Gas-miR36-5p from Gastrodia elata in an Alzheimer's Disease Model by Regulating Glycogen Synthase Kinase-3β
    Lu, Zhongteng
    Fu, Jianyuan
    Wu, Guang
    Yang, Zhecheng
    Wu, Xiaoqi
    Wang, Dan
    You, Zhengying
    Nie, Zuoming
    Sheng, Qing
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (24)
  • [43] Glycogen synthase kinase-3β: a novel therapeutic target for pancreatic cancer
    Ding, Li
    Billadeau, Daniel D.
    EXPERT OPINION ON THERAPEUTIC TARGETS, 2020, 24 (05) : 417 - 426
  • [44] Studies of glycogen synthase kinase-3 inhibitors
    Zhang Na
    Jiang Yongjun
    Yu Qingsen
    Zou Jianwei
    PROGRESS IN CHEMISTRY, 2007, 19 (04) : 614 - 623
  • [45] Glycogen synthase kinase 3β and Alzheimer's disease:: pathophysiological and therapeutic significance
    Balaraman, Y.
    Limaye, A. R.
    Levey, A. I.
    Srinivasan, S.
    CELLULAR AND MOLECULAR LIFE SCIENCES, 2006, 63 (11) : 1226 - 1235
  • [46] Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance
    Y. Balaraman
    A. R. Limaye
    A. I. Levey
    S. Srinivasan
    Cellular and Molecular Life Sciences CMLS, 2006, 63 : 1226 - 1235
  • [47] Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3β inhibitors through virtual screening
    Zhang, Peng
    Hu, Hai-Rong
    Huang, Zhao-Hui
    Lei, Jia-Yi
    Chu, Yong
    Ye, De-Yong
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (23) : 7232 - 7236
  • [48] Glycogen Synthase Kinase-3 as a Therapeutic Target for Cognitive Dysfunction in Neuropsychiatric Disorders
    O'Leary, Olivia
    Nolan, Yvonne
    CNS DRUGS, 2015, 29 (01) : 1 - 15
  • [49] Glycogen synthase kinase-3β (GSK3β) expression in a mouse model of Alzheimer's disease: A light and electron microscopy study
    Gandy, Johanna C.
    Melendez-Ferro, Miguel
    Bijur, Gautam N.
    Van Leuven, Fred
    Roche, Joy K.
    Lechat, Benoit
    Devijver, Herman
    Demedts, David
    Perez-Costas, Emma
    Roberts, Rosalinda C.
    SYNAPSE, 2013, 67 (06) : 313 - 327
  • [50] Glycogen synthase kinase-3 regulation of urinary concentrating ability
    Rao, Reena
    CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 2012, 21 (05) : 541 - 546