Altered adhesion efficiency and fibronectin content in fibroblasts from schizophrenic patients

Miyamae, Yasuyuki; Nakamura, Yu; Kashiwagi, Yujiro; Tanaka, Toshihisa; Kudo, Takashi; Takeda, Masatoshi

doi:10.1046/j.1440-1819.1998.00386.x

Cited by 18 publications

(11 citation statements)

References 31 publications

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“…Fibronectin is a high molecular weight ECM glycoprotein that binds to integrin receptors and plays important roles in neuro- and synaptogenesis. Dysregulation of fibronectin may result in neurodevelopmental abnormalities related to the pathogenesis of Sz [58, 59]. In contrast, a study showed no significant association of fibronectin with Sz [60].…”

Section: Changes In Brain Ecm In Neurodegenerative Conditionsmentioning

confidence: 99%

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Sethi

Zaia

2016

Anal Bioanal Chem

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Brain extracellular matrix (ECM) is a highly organized system that consists of collagens, non-collagenous proteins, glycoproteins, hyaluronan and proteoglycans (PGs). Recognized physiological roles of ECM include developmental regulation, tissue homeostasis, cell migration, proliferation, differentiation, neuronal plasticity, and neurite outgrowth. Aberrant ECM structure is associated with brain neurodegenerative conditions. This review focuses on two neurodegenerative conditions, schizophrenia (Sz) and Alzheimer's disease (AD), and summarizes recent findings of altered ECM components, including PGs, glycosaminoglycans (GAGs), proteins and glycoproteins, and proteins and genes related to other brain components. The scope includes immunohistochemical, genomics, transcriptomics, proteomics and glycomics studies, and a critical assessment of current state of proteomics studies for neurodegenerative disorders. The intent is to summarize the ECM molecular alterations associated with neurodegenerative pathophysiology.

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Section: Changes In Brain Ecm In Neurodegenerative Conditionsmentioning

confidence: 99%

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Sethi

Zaia

2016

Anal Bioanal Chem

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“…Of paramount importance, the field requires pragmatic methods that can readily derive large numbers of relevant cells from multiple cases and controls, which are needed to represent the spectrum of variability between individuals. Accessible non-neural cells like skin fibroblasts or transformed lymphocytes have been used to identify differences in cell biology associated with schizophrenia (SZ) and Parkinson's disease (PD) (Mahadik and Mukherjee, 1996;Miyamae et al, 1998;WinklerStuck et al, 2004;Hoepken et al, 2008) but the utility of non-neural cells for understanding the cellular bases of neurological and neuropsychiatric disorders is limited (Matigian et al, 2008). Another approach is to develop stem cell models of disease: embryonic stem (ES) cells carrying genetic mutations have been isolated after pre-implantation genetic diagnosis (Verlinsky et al, 2005;Mateizel et al, 2006), and induced pluripotent stem (iPS) cells have been generated from patients, including those with PD (Park et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Disease-specific, neurosphere-derived cells as models for brain disorders

Matigian

Abrahamsen

Sutharsan

et al. 2010

Disease Models &Amp; Mechanisms

187

237

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SUMMARYThere is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.

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“…Cancer is not the only disease related to FAK dysregulation. Early reports pointed to decreased adhesion efficiency in fibroblasts of schizophrenic patients (Miyamae et al, 1998), although the localization and amount of FAK in these cells was not observed to change. Only recently it was demonstrated that focal adhesion dynamics and FAK expression are dysregulated in olfactory mucosa neurospheres obtained from schizophrenia patients (Fan et al, 2013).…”

Section: A Role For Fak In Neurological Diseasesmentioning

confidence: 82%

The diverse roles and multiple forms of focal adhesion kinase in brain

Armendáriz

Masdeu

Soriano

et al. 2014

Eur J of Neuroscience

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Although it was originally characterized as a constituent of focal adhesions in fibroblasts, focal adhesion kinase (FAK) is now considered to be not only a mediator of adhesion processes but also a crucial regulator of guidance and a modulator of gene expression. FAK is the main transducer of the integrin signaling required to stabilize the actin cytoskeleton. However, additional activities have been described over the years. In the brain, FAK deserves particular attention as it is found in various alternatively spliced forms - these distributed in multiple subcellular compartments or bound to multiple partners. Moreover, its signaling involves not only phosphorylation but also ubiquitination and proteolysis. Several experimental cell models demonstrate that FAK increases or decreases migration, participates in differentiation and contributes to plasticity events. In addition, this kinase is linked to cell survival in cancer and apoptosis. This review focuses on the diversity of events involving brain-located forms of FAK.

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Altered adhesion efficiency and fibronectin content in fibroblasts from schizophrenic patients

Cited by 18 publications

References 31 publications

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Disease-specific, neurosphere-derived cells as models for brain disorders

The diverse roles and multiple forms of focal adhesion kinase in brain

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