a Department of Molecular Physiology and Neurobiology , University of Wroclaw , Wroclaw , Poland.
b Department of Microbiology and Immunology , Brody School of Medicine at East Carolina University , Greenville , NC , USA.
Expert Opin Ther Targets. 2018 Oct;22(10):833-848. doi: 10.1080/14728222.2018.1526925. Epub 2018 Sep 26.
Glycogen synthase kinase 3 (GSK3) is at the center of cellular signaling and controls various aspects of brain functions, including development of the nervous system, neuronal plasticity and onset of neurodegenerative disorders. Areas covered: In this review, recent efforts in elucidating the roles of GSK3 in neuronal plasticity and development of brain pathologies; Alzheimer's and Parkinson's disease, schizophrenia, and age-related neurodegeneration are described. The effect of microglia and astrocytes on development of the pathological states is also discussed. Expert opinion: GSK3β and its signaling pathway partners hold great promise as therapeutic target(s) for a multitude of neurological disorders. Activity of the kinase is often elevated in brain disorders. However, due to the wide range of GSK3 cellular targets, global inhibition of the kinase leads to severe side-effects and GSK3 inhibitors rarely reach Phase-2 clinical trials. Thus, a selective modulation of a specific cellular pool of GSK3 or specific down- or upstream partners of the kinase might provide more efficient anti-neurodegenerative therapies.
糖原合酶激酶 3（GSK3）处于细胞信号的中心，控制着大脑功能的各个方面，包括神经系统的发育、神经元可塑性和神经退行性疾病的发作。
在这篇综述中，描述了最近在阐明 GSK3 在神经元可塑性和脑病理学发展中的作用方面的努力；阿尔茨海默病和帕金森病、精神分裂症和与年龄相关的神经退行性变。还讨论了小胶质细胞和星形胶质细胞对病理性状态发展的影响。
GSK3β及其信号通路伙伴作为治疗多种神经疾病的治疗靶点具有很大的潜力。激酶的活性在大脑疾病中常常升高。然而，由于 GSK3 细胞靶标的广泛范围，激酶的全局抑制会导致严重的副作用，GSK3 抑制剂很少能进入 2 期临床试验。因此，对激酶的特定细胞池或特定上下游伙伴的选择性调节可能提供更有效的抗神经退行性治疗。
