期刊
EXPERT OPINION ON THERAPEUTIC TARGETS
卷 22, 期 10, 页码 833-848出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2018.1526925
关键词
Synaptic plasticity; brain aging; inflammation; Alzheimer's disease; Parkinson's disease; schizophrenia; astrocytes
资金
- Polish Ministry of Science and Higher Education [UMO-2015/19/B/NZ1/00332]
- East Carolina University [111104, 111110-668715-0000]
Introduction: 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: GSK3 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.
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