Development of mouse fibroblast cell line expressing human tau protein and evaluation of tau-dependent cytotoxity

Klenyaeva, A. N.; Chuprov‐Netochin, Roman N.; Marusich, Elena; Tatarnikova, Olga; Orlov, M. A.; Бобкова, Н. В.

doi:10.1134/s1990747814020111

Cited by 2 publications

(3 citation statements)

References 25 publications

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“…In contrast, when these fibrils were injected into mice hippocampus the classic tangle patterns appeared. Since similar punctuated patterns of p-Tau immunostaining have been reported in lymphocytes ( 36 ), fibroblasts ( 37 ), and skin cells ( 18 ), this indicates a distinctive feature of p-Tau in no-neural tissue, and it may be related to different functions of Tau in peripheral tissue. Also, immunocytochemistry confirmed the same pattern and localization of p-Tau (Figures 2 and 3 ).…”

Section: Discussionsupporting

confidence: 77%

Tau Protein in Oral Mucosa and Cognitive State: A Cross-sectional Study

et al. 2017

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Neurodegenerative diseases are characterized by the presence of abnormal aggregates of proteins in brain tissue. Among them, the presence of aggregates of phosphorylated Tau protein (p-Tau) is the hallmark of Alzheimer’s disease (AD) and other major neurodegenerative disorders such as corticobasal degeneration and frontotemporal dementia among others. Although Tau protein has previously been assumed to be exclusive to the central nervous system, it is also found in peripheral tissues. The purpose of this study was to determine whether there is a differential Tau expression in oral mucosa cells according to cognitive impairment. Eighty-one subjects were enrolled in the study and classified per Mini-Mental State Examination test score into control, mild cognitive impairment (MCI), and severe cognitive impairment (SCI) groups. Immunocytochemistry and immunofluorescence revealed the presence of Tau and four p-Tau forms in the cytoplasm and nucleus of oral mucosa cells. More positivity was present in subjects with cognitive impairment than in control subjects, both in the nucleus and cytoplasm, in a speckle pattern. The mRNA expression of Tau by quantitative real-time polymerase chain reaction was higher in SCI as compared with the control group (P < 0.01). A significantly higher percentage of immunopositive cells in the SCI group was found via flow cytometry in comparison to controls and the MCI group (P < 0.01). These findings demonstrate the higher presence of p-Tau and Tau transcript in the oral mucosa of cognitively impaired subjects when compared with healthy subjects. The feasibility of p-Tau quantification by flow cytometry supports the prospective analysis of oral mucosa as a support tool for screening of proteinopathies in cognitively impaired patients.

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Section: Discussionsupporting

confidence: 77%

Tau Protein in Oral Mucosa and Cognitive State: A Cross-sectional Study

et al. 2017

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“…Taken together, the findings of the present study suggest that the phosphorylation state and accumulation levels along subcellular compartments of Tau are modified upon oxidative stress by mechanisms that remain to be characterized; which is in accordance with reports in neurons (Audrey et al, 2011 ). In fact the presence of hyperphosphorylated tau in mouse (Klenyaeva et al, 2014 ) and human (Corlier et al, 2015 ) fibroblasts has been described. It is believed that the tau protein plays an important role in the compensatory mechanisms of the cell upon oxidative stress and may mediate epigenetic mechanisms (Mastroeni et al, 2011 ; Frost et al, 2014 ; Sanchez-Mut and Gräff, 2015 ).…”

Section: Discussionmentioning

confidence: 98%

“…It is believed that the tau protein plays an important role in the compensatory mechanisms of the cell upon oxidative stress and may mediate epigenetic mechanisms (Mastroeni et al, 2011 ; Frost et al, 2014 ; Sanchez-Mut and Gräff, 2015 ). The fibroblasts model could serve as a system simulating the events occurring at the early stage of taupathies (Klenyaeva et al, 2014 ), thus this model will generate new insights on the tau protein mechanisms involved in the onset of neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress Modifies the Levels and Phosphorylation State of Tau Protein in Human Fibroblasts

et al. 2017

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Since the tau protein is closely involved in the physiopathology of Alzheimer's disease (AD), studying its behavior in cellular models might lead to new insights on understanding this devastating disease at molecular levels. In the present study, primary cultures of human fibroblasts were established and used to determine the expression and localization of the tau protein in distinct phosphorylation states in both untransfected and tau gene-transfected cells subjected to oxidative stress. Higher immunopositivity to phospho-tau was observed in cell nuclei in response to oxidative stress, while the levels of total tau in the cytosol remained unchanged. These findings were observed in both untransfected cells and those transfected with the tau gene. The present work represents a useful model for studying the physiopathology of AD at the cellular level in terms of tau protein implications.

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Development of mouse fibroblast cell line expressing human tau protein and evaluation of tau-dependent cytotoxity

Cited by 2 publications

References 25 publications

Tau Protein in Oral Mucosa and Cognitive State: A Cross-sectional Study

Tau Protein in Oral Mucosa and Cognitive State: A Cross-sectional Study

Oxidative Stress Modifies the Levels and Phosphorylation State of Tau Protein in Human Fibroblasts

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