Erratum to: Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes

Kondo, Takayuki; Funayama, Misato; Miyake, Michiyo; Tsukita, Kayoko; Era, Takumi; Osaka, Hitoshi; Ayaki, Takashi; Takahashi, Ryōsuke; Inoue, Haruhisa

doi:10.1186/s40478-016-0366-8

Cited by 3 publications

(3 citation statements)

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“…These findings revealed the fundamental physiological mechanism of Epilepsy caused by SCN1A loss-of-function mutations 117 . Simultaneously, the iPSCs model research confirmed that astrocyte activation 118 - 120 , mitochondrial dysfunction 121 , 122 , and abnormal signaling pathway activity 123 , 124 were also important factors to the molecular mechanisms of GE 108 .…”

Section: Application Of Ipscs In Epilepsymentioning

confidence: 74%

Great Expectations: Induced pluripotent stem cell technologies in neurodevelopmental impairments

Zhang

Liu

et al. 2021

Int. J. Med. Sci.

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Somatic cells such as skin fibroblasts, umbilical cord blood, peripheral blood, urinary epithelial cells, etc., are transformed into induced pluripotent stem cells (iPSCs) by reprogramming technology, a milestone in the stem-cell research field. IPSCs are similar to embryonic stem cells (ESCs), exhibiting the potential to differentiate into various somatic cells. Still, the former avoid problems of immune rejection and medical ethics in the study of ESCs and clinical trials. Neurodevelopmental disorders are chronic developmental brain dysfunctions that affect cognition, exercise, social adaptability, behavior, etc. Due to various inherited or acquired causes, they seriously affect the physical and psychological health of infants and children. These include generalized stunting / mental disability (GDD/ID), Epilepsy, autism spectrum disease (ASD), and attention deficit hyperactivity disorder (ADHD). Most neurodevelopmental disorders are challenging to cure. Establishing a neurodevelopmental disorder system model is essential for researching and treating neurodevelopmental disorders. At this stage, the scarcity of samples is a bigger problem for studying neurological diseases based on the donor, ethics, etc. Some iPSCs are reprogrammed from somatic cells that carry disease-causing mutations. They differentiate into nerve cells by induction, which has the original characteristics of diseases. Disease-specific iPSCs are used to study the mechanism and pathogenesis of neurodevelopmental disorders. The process provided samples and the impetus for developing drugs and developing treatment plans for neurodevelopmental disorders. Here, this article mainly introduced the development of iPSCs, the currently established iPSCs disease models, and artificial organoids related to neurodevelopmental impairments. This technology will promote our understanding of neurodevelopmental impairments and bring great expectations to children with neurological disorders.

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Section: Application Of Ipscs In Epilepsymentioning

confidence: 74%

Great Expectations: Induced pluripotent stem cell technologies in neurodevelopmental impairments

Zhang

Liu

et al. 2021

Int. J. Med. Sci.

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“…Patients with Alexander disease (AxD), associated with mutations in the glial fibrillary acidic protein gene ( GFAP ), develop a leukoencephalopathy with macrocephaly, seizures, and psychomotor retardation, which usually leads to death within the first decade . Kondo et al found that GFAP accumulates locally in patient‐derived glial cells, the Rosenthal‐fiber‐like structure in the intracellular area becomes entangled, and there are increases in N‐cadherin expression, mammalian target of rapamycin (mTOR) signaling pathway activity, and the release of cytokine and glutamate neurotransmitters . Recently, Ishii et al used iPSCs combined with single‐cell RNA transcription analysis technology and found that iPSC‐induced glial cells can enhance the activities of AMPA and NMDA receptors in excitatory neurons and increase their high‐frequency spontaneous discharges .…”

Section: Ipsc Studies On the Molecular Mechanisms Of Gementioning

confidence: 99%

Progress in the molecular mechanisms of genetic epilepsies using patient‐induced pluripotent stem cells

et al. 2018

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SummaryResearch findings on the molecular mechanisms of epilepsy almost always originate from animal experiments, and the development of induced pluripotent stem cell (iPSC) technology allows the use of human cells with genetic defects for studying the molecular mechanisms of genetic epilepsy (GE) for the first time. With iPSC technology, terminally differentiated cells collected from GE patients with specific genetic etiologies can be differentiated into many relevant cell subtypes that carry all of the GE patient's genetic information. iPSCs have opened up a new research field involving the pathogenesis of GE. Using this approach, studies have found that gene mutations induce GE by altering the balance between neuronal excitation and inhibition, which is associated. among other factors, with neuronal developmental disturbances, ion channel abnormalities, and synaptic dysfunction. Simultaneously, astrocyte activation, mitochondrial dysfunction, and abnormal signaling pathway activity are also important factors in the molecular mechanisms of GE.

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“…Although its mechanism is unknown, studies of cell lines and animal models had been suggested that AxD could activate stress response pathways within astrocytes due to increased expression of WT or mutant GFAP (12–17) that would potentially reduce proteasomal activity in cells (18) and due to oxidative stress potentially producing an antioxidant response mediated by the transcription factor Nrf2 (19, 20) However, although these models are able to replicate the astrocytic changes occurring in the disease, including formation of Rosenthal fibers, they have failed to reproduce myelin loss (21, 22). While AxD has historically been described as a disorder of myelin formation, with loss of myelin and oligodendrocytes appearing as demyelinated areas in MRI studies (23), the full mechanism underlying AxD is not yet well understood (24, 25). For that, other authors had proposed other possibilities (26).…”

Section: Introductionmentioning

confidence: 99%

Alexander Disease Mutations Produce Cells with Coexpression of Glial Fibrillary Acidic Protein and NG2 in Neurosphere Cultures and Inhibit Differentiation into Mature Oligodendrocytes

et al. 2017

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BackgroundAlexander disease (AxD) is a rare disease caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). The disease is characterized by presence of GFAP aggregates in the cytoplasm of astrocytes and loss of myelin.ObjectivesDetermine the effect of AxD-related mutations on adult neurogenesis.MethodsWe transfected different types of mutant GFAP into neurospheres using the nucleofection technique.ResultsWe find that mutations may cause coexpression of GFAP and NG2 in neurosphere cultures, which would inhibit the differentiation of precursors into oligodendrocytes and thus explain the myelin loss occurring in the disease. Transfection produces cells that differentiate into new cells marked simultaneously by GFAP and NG2 and whose percentage increased over days of differentiation. Increased expression of GFAP is due to a protein with an anomalous structure that forms aggregates throughout the cytoplasm of new cells. These cells display down-expression of vimentin and nestin. Up-expression of cathepsin D and caspase-3 in the first days of differentiation suggest that apoptosis as a lysosomal response may be at work. HSP27, a protein found in Rosenthal bodies, is expressed less at the beginning of the process although its presence increases in later stages.ConclusionOur findings seem to suggest that the mechanism of development of AxD may not be due to a function gain due to increase of GFAP, but to failure in the differentiation process may occur at the stage in which precursor cells transform into oligodendrocytes, and that possibility may provide the best explanation for the clinical and radiological images described in AxD.

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Erratum to: Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes

Cited by 3 publications

References 1 publication

Great Expectations: Induced pluripotent stem cell technologies in neurodevelopmental impairments

Great Expectations: Induced pluripotent stem cell technologies in neurodevelopmental impairments

Progress in the molecular mechanisms of genetic epilepsies using patient‐induced pluripotent stem cells

Alexander Disease Mutations Produce Cells with Coexpression of Glial Fibrillary Acidic Protein and NG2 in Neurosphere Cultures and Inhibit Differentiation into Mature Oligodendrocytes

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