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Wnt Signaling in Neurogenesis during Aging and Physical Activity.

Chen M, Do H - Brain Sci (2012)

Bottom Line: Relatively little is known, however, about how aging and physical activity affect the Wnt signaling pathway.Herein, we briefly review the salient features of neurogenesis in young and then in old adult animals.Then, we discuss Wnt signaling and review the very few in vitro and in vivo studies that have examined the Wnt signaling pathways in aging and physical activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, California State University, 5151 State University Drive, Los Angeles, CA 90032, USA. mchen@calstatela.edu.

ABSTRACT
Over the past decade, much progress has been made regarding our understanding of neurogenesis in both young and old animals and where it occurs throughout the lifespan, although the growth of new neurons declines with increasing age. In addition, physical activity can reverse this age-dependent decline in neurogenesis. Highly correlated with this decline is the degree of inter and intracellular Wnt signaling, the molecular mechanisms of which have only recently started to be elucidated. So far, most of what we know about intracellular signaling during/following exercise centers around the CREB/CRE initiated transcriptional events. Relatively little is known, however, about how aging and physical activity affect the Wnt signaling pathway. Herein, we briefly review the salient features of neurogenesis in young and then in old adult animals. Then, we discuss Wnt signaling and review the very few in vitro and in vivo studies that have examined the Wnt signaling pathways in aging and physical activity.

No MeSH data available.


Related in: MedlinePlus

(Left) Wnt signaling is turned off when the ligand, although secreted by nearby astrocytes or neuroprogenitor cells, is bound by various Wnt inhibitors, such as Wnt inhibitory factor (WIF) and secreted fzl-related proteins (SFRPs). The fzl receptor remains bound by disheveled (dsh1) and LRP5/6 is bound by Dickopf (DKK1)-kremen complex, which helps anchor the complex into the membrane. With adenomatous polyposis (APC) and axin bound to casein kinase 1 and GSK-3β, these two kinases can now phosphorylate β-catenin, which is then sequestered by ubiquitins with the help of β-Trcp. β-Catenin is then degraded in the proteosome. (Right) Wnt signaling is turned on when Wnt binds fzl and the LRP5/6 co-receptor, promoting axin to dissociate from APC and dsh1 to phosphorylate LRP5/6. Meanwhile, casein kinase 1 phosphorylates GSK-3β, thereby inactivating it. β-Catenin then accumulates in the cytoplasm, enters the nucleus, where it binds to TCF/LEF and co-activators, such as pygopus (Pygo), legless (lgs), and P300/CBP, leading to the transcription of Wnt target genes.
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brainsci-02-00745-f002: (Left) Wnt signaling is turned off when the ligand, although secreted by nearby astrocytes or neuroprogenitor cells, is bound by various Wnt inhibitors, such as Wnt inhibitory factor (WIF) and secreted fzl-related proteins (SFRPs). The fzl receptor remains bound by disheveled (dsh1) and LRP5/6 is bound by Dickopf (DKK1)-kremen complex, which helps anchor the complex into the membrane. With adenomatous polyposis (APC) and axin bound to casein kinase 1 and GSK-3β, these two kinases can now phosphorylate β-catenin, which is then sequestered by ubiquitins with the help of β-Trcp. β-Catenin is then degraded in the proteosome. (Right) Wnt signaling is turned on when Wnt binds fzl and the LRP5/6 co-receptor, promoting axin to dissociate from APC and dsh1 to phosphorylate LRP5/6. Meanwhile, casein kinase 1 phosphorylates GSK-3β, thereby inactivating it. β-Catenin then accumulates in the cytoplasm, enters the nucleus, where it binds to TCF/LEF and co-activators, such as pygopus (Pygo), legless (lgs), and P300/CBP, leading to the transcription of Wnt target genes.

Mentions: Low-density lipoprotein receptor-related protein 5/6 (LRP 5/6) are co-receptors of fzl and are critical for Wnt signaling, as deletion mutants of this co-receptor completely abolishes Wnt signaling [37]. Wnt binding causes a conformational change in fzl, resulting in recruitment of dsh1 to the cytoplasmic tail of the receptor through its intracellular KTxxxW motif [37]. Wnt also causes the phosphorylation of dsh1 through activation of, perhaps, casein kinase 1, as well as of LRP5/6 whose C-terminus then reacts with axin, which is a downstream inhibitory component of the Wnt cascade. As axin is mobilized to the cell membrane, its activity is inhibited, resulting in the stabilization of β-catenin (Figure 2). Additionally, Wnt binding to fzl induces the phosphorylation of LRP 5/6 at two sites, one of which creates a docking site for axin, while the other is phosphorylated at the N-terminus by casein kinase 1 [37].


Wnt Signaling in Neurogenesis during Aging and Physical Activity.

Chen M, Do H - Brain Sci (2012)

(Left) Wnt signaling is turned off when the ligand, although secreted by nearby astrocytes or neuroprogenitor cells, is bound by various Wnt inhibitors, such as Wnt inhibitory factor (WIF) and secreted fzl-related proteins (SFRPs). The fzl receptor remains bound by disheveled (dsh1) and LRP5/6 is bound by Dickopf (DKK1)-kremen complex, which helps anchor the complex into the membrane. With adenomatous polyposis (APC) and axin bound to casein kinase 1 and GSK-3β, these two kinases can now phosphorylate β-catenin, which is then sequestered by ubiquitins with the help of β-Trcp. β-Catenin is then degraded in the proteosome. (Right) Wnt signaling is turned on when Wnt binds fzl and the LRP5/6 co-receptor, promoting axin to dissociate from APC and dsh1 to phosphorylate LRP5/6. Meanwhile, casein kinase 1 phosphorylates GSK-3β, thereby inactivating it. β-Catenin then accumulates in the cytoplasm, enters the nucleus, where it binds to TCF/LEF and co-activators, such as pygopus (Pygo), legless (lgs), and P300/CBP, leading to the transcription of Wnt target genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061808&req=5

brainsci-02-00745-f002: (Left) Wnt signaling is turned off when the ligand, although secreted by nearby astrocytes or neuroprogenitor cells, is bound by various Wnt inhibitors, such as Wnt inhibitory factor (WIF) and secreted fzl-related proteins (SFRPs). The fzl receptor remains bound by disheveled (dsh1) and LRP5/6 is bound by Dickopf (DKK1)-kremen complex, which helps anchor the complex into the membrane. With adenomatous polyposis (APC) and axin bound to casein kinase 1 and GSK-3β, these two kinases can now phosphorylate β-catenin, which is then sequestered by ubiquitins with the help of β-Trcp. β-Catenin is then degraded in the proteosome. (Right) Wnt signaling is turned on when Wnt binds fzl and the LRP5/6 co-receptor, promoting axin to dissociate from APC and dsh1 to phosphorylate LRP5/6. Meanwhile, casein kinase 1 phosphorylates GSK-3β, thereby inactivating it. β-Catenin then accumulates in the cytoplasm, enters the nucleus, where it binds to TCF/LEF and co-activators, such as pygopus (Pygo), legless (lgs), and P300/CBP, leading to the transcription of Wnt target genes.
Mentions: Low-density lipoprotein receptor-related protein 5/6 (LRP 5/6) are co-receptors of fzl and are critical for Wnt signaling, as deletion mutants of this co-receptor completely abolishes Wnt signaling [37]. Wnt binding causes a conformational change in fzl, resulting in recruitment of dsh1 to the cytoplasmic tail of the receptor through its intracellular KTxxxW motif [37]. Wnt also causes the phosphorylation of dsh1 through activation of, perhaps, casein kinase 1, as well as of LRP5/6 whose C-terminus then reacts with axin, which is a downstream inhibitory component of the Wnt cascade. As axin is mobilized to the cell membrane, its activity is inhibited, resulting in the stabilization of β-catenin (Figure 2). Additionally, Wnt binding to fzl induces the phosphorylation of LRP 5/6 at two sites, one of which creates a docking site for axin, while the other is phosphorylated at the N-terminus by casein kinase 1 [37].

Bottom Line: Relatively little is known, however, about how aging and physical activity affect the Wnt signaling pathway.Herein, we briefly review the salient features of neurogenesis in young and then in old adult animals.Then, we discuss Wnt signaling and review the very few in vitro and in vivo studies that have examined the Wnt signaling pathways in aging and physical activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, California State University, 5151 State University Drive, Los Angeles, CA 90032, USA. mchen@calstatela.edu.

ABSTRACT
Over the past decade, much progress has been made regarding our understanding of neurogenesis in both young and old animals and where it occurs throughout the lifespan, although the growth of new neurons declines with increasing age. In addition, physical activity can reverse this age-dependent decline in neurogenesis. Highly correlated with this decline is the degree of inter and intracellular Wnt signaling, the molecular mechanisms of which have only recently started to be elucidated. So far, most of what we know about intracellular signaling during/following exercise centers around the CREB/CRE initiated transcriptional events. Relatively little is known, however, about how aging and physical activity affect the Wnt signaling pathway. Herein, we briefly review the salient features of neurogenesis in young and then in old adult animals. Then, we discuss Wnt signaling and review the very few in vitro and in vivo studies that have examined the Wnt signaling pathways in aging and physical activity.

No MeSH data available.


Related in: MedlinePlus