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DISC1-related signaling pathways in adult neurogenesis of the hippocampus
Authors:Qian Wu  Yi Li  Bo Xiao
Affiliation:Department of Neurology, Xiangya Hospital, Central South University, 87 Xiang Ya Road, Changsha, Hunan, 410008, China
Abstract:Disrupted-in-schizophrenia 1 (DISC1) is a multifunctional scaffold protein which plays an important role in neurogenesis and neural development in the adult brain, especially in the dentate gyrus (DG) of the hippocampus. Accumulated research has unveiled the role of DISC1 in several aspects of neural development and neurogenesis, such as neuronal maturation, proliferation, migration, positioning, differentiation, dendritic growth, axonal outgrowth, and synaptic plasticity. Studies on the function of this protein have explored multiple facets, including variants and missense mutants in genetics, proteins interactivity and signaling pathways in molecular biology, and pathogenesis and treatment targets of major mental illness, and more. In this review, we present several signaling pathways discussed in recent research, such as the AKT signaling pathway, GABA signaling pathway, GSK3β signaling pathway, Wnt signaling pathway, and NMDA-R signaling pathway. DISC1 interacts, directly or indirectly, with these signaling pathways and they co-regulate the process of adult neurogenesis in the hippocampus.
Keywords:BP, Bipolar disorder   CA, Cornu ammonis   CNS, Central nervous system   CPP, 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid   CT, Carboxyterminal   DG, Dentate gyrus   DGCs, Dentate granule cells   DISC, Disrupted-in-schizophrenia 1   Dixdc1, Dix domain containing 1   FEZ1, Elongation Protein Zeta-1   Fz, Frizzled   GABA, γ-aminobutyric acid   Grb2, Growth factor receptor bound protein 2   GSK3β, Glycogen synthase kinase 3β   KCC2, K+&ndash  Cl&minus   co-transporter 2   kDa, kilodalton   KIF5B, Kinesin family members 5B   LEF/TCF, Lymphoid enhancer factor/T cell factor   LIS1, Lissencephaly-1   LRP5/6, Lipoprotein receptor-related protein 5/6   MDD, Major depressive disorder   MK-801, (5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]c-cyclohepten-5-10-imine hydrogen maleate   MW, Molecular weight   NDEL1, Nuclear distribution gene E-like homolog 1   NKCC1, Na+-K+-Cl&minus   co-transporter1   NLS, Nuclear localization signal   NMDA-R, N-methyl-d-aspartate-type glutamate receptor   NSCs, Neural stem cells   NT, Unique amino   NT-3, Neutrophins-3   OB, Olfactory bulbs   PTEN, Phosphatase and tensin homolog deleted on chromosome ten   RNAi, RNA interference   RYK, Related to tyrosine kinase   SGZ, Subgranular zone   shRNA, Short hairpin RNA   siRNA, Small interference RNA   SVZ, Subventricular zone   SZ, Schizophrenia
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