Amyloid-β Precursor Protein Induces Glial Differentiation of Neural Progenitor Cells by Activation of the IL-6/gp130 Signaling Pathway

Kwak, Young-Don; Dantuma, Elise; Merchant, Stephanie; Bushnev, Sergey; Sugaya, Kiminobu

doi:10.1007/978-1-4614-0785-0_12

Cited by 9 publications

(15 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of in vitro studies have attempted to shed light on the physiological functions of sAPP in the brain, showing that sAPP enhances synaptogenesis, neurite outgrowth, cell survival, adhesion, and proliferation of embryonic neural stem cells (56,57). In addition, recent in vitro and in vivo evidence shows that sAPP administration promotes astrogliogenesis (21,22,47). Our findings suggest that high levels of sAPP or cell surface-associated APP have a role in the increased astrocytic differentiation that characterizes trisomic NPCs.…”

Section: The App/aicd-dependent Alteration Of the Shh Pathway Impairssupporting

confidence: 57%

“…9). JAK1 and gp130 belong to the transcriptional targets of STAT3, and consequently, the IL-6 cytokine-related pathway is efficiently modulated by an auto-regulatory positive loop (47). We found that although STAT3 gene expression levels were similar in trisomic and control NPC cultures (Fig.…”

Section: Increased Levels Of Sapp In Neuronal Precursor Cell Culturesmentioning

confidence: 70%

“…It has recently been shown that sAPP␣ overexpression may result in enhancement of the Notch pathway (46) as well as of the IL-6 cytokine-related pathway (47), which are crucial for the acquisition of a glial phenotype (48,49). To identify the mechanism(s) by which sAPP increases astrogliogenesis in trisomic NPCs, we examined gene expression of various molecules downstream from the Notch and IL-6 cytokine-related pathways.…”

Section: Increased Levels Of Sapp In Neuronal Precursor Cell Culturesmentioning

confidence: 99%

“…Ngn1, Ngn2, and DNA methylation) factors. A recent study has revealed that the IL-6/gp130 signaling pathway plays a pivotal role in astrocyte differentiation of NPCs (47). Based on this evidence, it has been postulated that sAPP may affect the cell fate of neural precursor cells in DS via the activation of the IL-6/gp130 signaling pathway (47).…”

Section: The App/aicd-dependent Alteration Of the Shh Pathway Impairsmentioning

confidence: 99%

“…A recent study has revealed that the IL-6/gp130 signaling pathway plays a pivotal role in astrocyte differentiation of NPCs (47). Based on this evidence, it has been postulated that sAPP may affect the cell fate of neural precursor cells in DS via the activation of the IL-6/gp130 signaling pathway (47). Our data confirm this suggestion, showing that increased levels of APP/sAPP in trisomic NPCs enhance the acquisition of an astrocytic phenotype via the activation of the IL-6/gp130 signaling pathway.…”

Section: The App/aicd-dependent Alteration Of the Shh Pathway Impairsmentioning

confidence: 99%

See 4 more Smart Citations

The Amyloid Precursor Protein (APP) Triplicated Gene Impairs Neuronal Precursor Differentiation and Neurite Development through Two Different Domains in the Ts65Dn Mouse Model for Down Syndrome

Trazzi¹,

Fuchs²,

Valli

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Individuals with Down syndrome suffer from mental retardation due to severe neurogenesis impairment. Results: Normalization of the triplicated gene APP expression restores neuronal maturation and differentiation in trisomic neuronal precursors. Conclusion: APP overproduction contributes to neurogenesis impairment in DS.Significance: APP signaling may be a target for therapeutic approaches aiming to improve brain development in DS.

show abstract

Section: The App/aicd-dependent Alteration Of the Shh Pathway Impairssupporting

confidence: 57%

Section: Increased Levels Of Sapp In Neuronal Precursor Cell Culturesmentioning

confidence: 70%

Section: Increased Levels Of Sapp In Neuronal Precursor Cell Culturesmentioning

confidence: 99%

Section: The App/aicd-dependent Alteration Of the Shh Pathway Impairsmentioning

confidence: 99%

Section: The App/aicd-dependent Alteration Of the Shh Pathway Impairsmentioning

confidence: 99%

See 3 more Smart Citations

The Amyloid Precursor Protein (APP) Triplicated Gene Impairs Neuronal Precursor Differentiation and Neurite Development through Two Different Domains in the Ts65Dn Mouse Model for Down Syndrome

Trazzi¹,

Fuchs²,

Valli

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

GFAP expression and social deficits in transgenic mice overexpressing human sAPPα

Bailey

Hou

Song

et al. 2013

Glia

View full text Add to dashboard Cite

Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPα protein is neurotrophic and neuroprotective and recently showed a correlation to glial differentiation in human neural stem cells (NSCs) via the IL-6 pathway. Considering evidence of gliosis in postmortem autistic brains, we hypothesized that subsets of patients with autism would exhibit elevations in CNS sAPPα and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior. Elevations in sAPPα levels were observed in brains of autistic patients compared to controls. Transgenic mice engineered to overexpress human sAPPα (TgsAPPα mice) displayed hypoactivity, impaired sociability, increased brain glial fibrillary acidic protein (GFAP) expression, and altered Notch1 and IL-6 levels. NSCs isolated from TgsAPPα mice, and those derived from wild-type mice treated with sAPPα, displayed suppressed β-tubulin III and elevated GFAP expression. These results suggest that elevations in brain sAPPα levels are observed in subsets of individuals with autism and TgsAPPα mice display signs suggestive of gliosis and behavioral impairment.

show abstract

Analysis of pro‐ and anti‐inflammatory cytokine gene variants and serum cytokine levels as prognostic markers in breast cancer

Kaur

Vasudeva

Singla

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

The aim of current study was to evaluate the genetic variation in all the genes encoding pro- and anti-inflammatory cytokines in association with breast cancer development in patients from Malwa region of Punjab. The importance of the levels of interleukin (IL)-17, tumor necrosis factor, interferon γ, IL-10, IL-6, IL-4, and IL-2 with respect to clinicopathological data, prognosis, and disease-free survival was also determined in these patients. Two hundred and fifty female breast cancer patients and 250 age-matched controls were screened for variations in cytokine-encoding genes using global screening array microchip. The level of cytokines was estimated in 150 patients and 60 age-matched controls using BD™ Cytometric Bead Array (CBA) Human Th1/Th2/Th17 cytokine kit by BD Accuri flow cytometer. The difference in cytokine levels was evaluated by Mann-Whitney test. No significant variation in the genes encoding various cytokines was found between patients and controls. Out of the seven cytokines evaluated, the levels of IL-6 and IL-17a were found to be significantly high in patients in comparison with controls ( p = 0.001 and 0.02, respectively). The elevated levels of these cytokines are also associated significantly with poor outcome. We did not find any specific variation in the genes encoding various cytokines between patients and controls. However, there was a significant difference in the serum levels of IL-6 and IL-17a between patients and controls, and the elevated levels of these two cytokines associated significantly with poor outcome in breast cancer patients and, therefore, can be used as prognostic markers.

show abstract

Amyloid-β Precursor Protein Induces Glial Differentiation of Neural Progenitor Cells by Activation of the IL-6/gp130 Signaling Pathway

Cited by 9 publications

References 39 publications

The Amyloid Precursor Protein (APP) Triplicated Gene Impairs Neuronal Precursor Differentiation and Neurite Development through Two Different Domains in the Ts65Dn Mouse Model for Down Syndrome

The Amyloid Precursor Protein (APP) Triplicated Gene Impairs Neuronal Precursor Differentiation and Neurite Development through Two Different Domains in the Ts65Dn Mouse Model for Down Syndrome

GFAP expression and social deficits in transgenic mice overexpressing human sAPPα

Analysis of pro‐ and anti‐inflammatory cytokine gene variants and serum cytokine levels as prognostic markers in breast cancer

Contact Info

Product

Resources

About