Altered growth factor signaling pathways as the basis of aberrant stem cell maturation in schizophrenia

In recent years evidence has accumulated that the activity of the signaling cascades of Neuregulin-1, Wnt, TGF-beta, BDNF-p75 and DISC1 is different between control subjects and patients with schizophrenia. These pathways are involved in embryonic and adult neurogenesis and neuronal maturation. A re...

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Published inPharmacology & therapeutics (Oxford) Vol. 121; no. 1; pp. 115 - 122
Main Author Kalkman, Hans O.
Format Journal Article
LanguageEnglish
Published England 01.01.2009
Subjects
Age Determination by Skeleton
Animals
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - metabolism
Brain-Derived Neurotrophic Factor - physiology
Cell Differentiation - physiology
Humans
Intercellular Signaling Peptides and Proteins - physiology
Mice
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Neuregulin-1
Neurogenesis
Receptor, Epidermal Growth Factor - genetics
Receptor, Epidermal Growth Factor - metabolism
Receptor, Epidermal Growth Factor - physiology
Receptor, ErbB-4
Receptors, Nerve Growth Factor - genetics
Receptors, Nerve Growth Factor - metabolism
Receptors, Nerve Growth Factor - physiology
Risk Factors
Schizophrenia - metabolism
Schizophrenia - physiopathology
Signal Transduction - physiology
Stem Cells - physiology
Telomere
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - metabolism
Transforming Growth Factor beta - physiology
Wnt Proteins - genetics
Wnt Proteins - metabolism
Wnt Proteins - physiology
Online AccessGet full text
ISSN0163-7258
DOI10.1016/j.pharmthera.2008.11.002

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Abstract In recent years evidence has accumulated that the activity of the signaling cascades of Neuregulin-1, Wnt, TGF-beta, BDNF-p75 and DISC1 is different between control subjects and patients with schizophrenia. These pathways are involved in embryonic and adult neurogenesis and neuronal maturation. A review of the clinical data indicates that in schizophrenia the Wnt pathway is most likely hypoactive, whereas the Nrg1-ErbB4, the TGF-beta- and the BDNF-p75-pathways are hyperactive. Haplo-insuffiency of the DISC1 gene is currently the best established schizophrenia risk factor. Preclinical experiments indicate that suppression of DISC1 signaling leads to accelerated dendrite development in neuronal stem cells, accelerated migration and aberrant integration into the neuronal network. Other preclinical experiments show that increasing NRG1-, BDNF- and TGF-beta signaling and decreasing Wnt signaling, also promotes adult neuronal differentiation and migration. Thus deviations in these pathways detected in schizophrenia could contribute to premature neuronal differentiation, accelerated migration and inappropriate insertion into the neuronal network. Initial clinical findings are confirmatory: neuronal stem cells isolated from nasal biopsies from schizophrenia patients display signs of accelerated development, whilst increased erosion of telomeres and bone age provide further support for accelerated cell maturation in schizophrenia.
AbstractList In recent years evidence has accumulated that the activity of the signaling cascades of Neuregulin-1, Wnt, TGF- beta , BDNF-p75 and DISC1 is different between control subjects and patients with schizophrenia. These pathways are involved in embryonic and adult neurogenesis and neuronal maturation. A review of the clinical data indicates that in schizophrenia the Wnt pathway is most likely hypoactive, whereas the Nrg1-ErbB4, the TGF- beta - and the BDNF-p75-pathways are hyperactive. Haplo-insuffiency of the DISC1 gene is currently the best established schizophrenia risk factor. Preclinical experiments indicate that suppression of DISC1 signaling leads to accelerated dendrite development in neuronal stem cells, accelerated migration and aberrant integration into the neuronal network. Other preclinical experiments show that increasing NRG1-, BDNF- and TGF- beta signaling and decreasing Wnt signaling, also promotes adult neuronal differentiation and migration. Thus deviations in these pathways detected in schizophrenia could contribute to premature neuronal differentiation, accelerated migration and inappropriate insertion into the neuronal network. Initial clinical findings are confirmatory: neuronal stem cells isolated from nasal biopsies from schizophrenia patients display signs of accelerated development, whilst increased erosion of telomeres and bone age provide further support for accelerated cell maturation in schizophrenia.
In recent years evidence has accumulated that the activity of the signaling cascades of Neuregulin-1, Wnt, TGF-beta, BDNF-p75 and DISC1 is different between control subjects and patients with schizophrenia. These pathways are involved in embryonic and adult neurogenesis and neuronal maturation. A review of the clinical data indicates that in schizophrenia the Wnt pathway is most likely hypoactive, whereas the Nrg1-ErbB4, the TGF-beta- and the BDNF-p75-pathways are hyperactive. Haplo-insuffiency of the DISC1 gene is currently the best established schizophrenia risk factor. Preclinical experiments indicate that suppression of DISC1 signaling leads to accelerated dendrite development in neuronal stem cells, accelerated migration and aberrant integration into the neuronal network. Other preclinical experiments show that increasing NRG1-, BDNF- and TGF-beta signaling and decreasing Wnt signaling, also promotes adult neuronal differentiation and migration. Thus deviations in these pathways detected in schizophrenia could contribute to premature neuronal differentiation, accelerated migration and inappropriate insertion into the neuronal network. Initial clinical findings are confirmatory: neuronal stem cells isolated from nasal biopsies from schizophrenia patients display signs of accelerated development, whilst increased erosion of telomeres and bone age provide further support for accelerated cell maturation in schizophrenia.In recent years evidence has accumulated that the activity of the signaling cascades of Neuregulin-1, Wnt, TGF-beta, BDNF-p75 and DISC1 is different between control subjects and patients with schizophrenia. These pathways are involved in embryonic and adult neurogenesis and neuronal maturation. A review of the clinical data indicates that in schizophrenia the Wnt pathway is most likely hypoactive, whereas the Nrg1-ErbB4, the TGF-beta- and the BDNF-p75-pathways are hyperactive. Haplo-insuffiency of the DISC1 gene is currently the best established schizophrenia risk factor. Preclinical experiments indicate that suppression of DISC1 signaling leads to accelerated dendrite development in neuronal stem cells, accelerated migration and aberrant integration into the neuronal network. Other preclinical experiments show that increasing NRG1-, BDNF- and TGF-beta signaling and decreasing Wnt signaling, also promotes adult neuronal differentiation and migration. Thus deviations in these pathways detected in schizophrenia could contribute to premature neuronal differentiation, accelerated migration and inappropriate insertion into the neuronal network. Initial clinical findings are confirmatory: neuronal stem cells isolated from nasal biopsies from schizophrenia patients display signs of accelerated development, whilst increased erosion of telomeres and bone age provide further support for accelerated cell maturation in schizophrenia.
Author Kalkman, Hans O.
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Snippet In recent years evidence has accumulated that the activity of the signaling cascades of Neuregulin-1, Wnt, TGF-beta, BDNF-p75 and DISC1 is different between...
In recent years evidence has accumulated that the activity of the signaling cascades of Neuregulin-1, Wnt, TGF- beta , BDNF-p75 and DISC1 is different between...
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StartPage 115
SubjectTerms Age Determination by Skeleton
Animals
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - metabolism
Brain-Derived Neurotrophic Factor - physiology
Cell Differentiation - physiology
Humans
Intercellular Signaling Peptides and Proteins - physiology
Mice
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Neuregulin-1
Neurogenesis
Receptor, Epidermal Growth Factor - genetics
Receptor, Epidermal Growth Factor - metabolism
Receptor, Epidermal Growth Factor - physiology
Receptor, ErbB-4
Receptors, Nerve Growth Factor - genetics
Receptors, Nerve Growth Factor - metabolism
Receptors, Nerve Growth Factor - physiology
Risk Factors
Schizophrenia - metabolism
Schizophrenia - physiopathology
Signal Transduction - physiology
Stem Cells - physiology
Telomere
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - metabolism
Transforming Growth Factor beta - physiology
Wnt Proteins - genetics
Wnt Proteins - metabolism
Wnt Proteins - physiology
Title Altered growth factor signaling pathways as the basis of aberrant stem cell maturation in schizophrenia
URI https://www.ncbi.nlm.nih.gov/pubmed/19046988
https://www.proquest.com/docview/20602400
https://www.proquest.com/docview/66777228
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