pubmed: alzheimer's and stem...
NCBI: db=pubmed; Term=alzheimer's and stem cell therapy
NCBI pubmed
  • Multitasking Microglia and Alzheimer's Disease: Diversity, Tools and Therapeutic Targets.
    Related Articles

    Multitasking Microglia and Alzheimer's Disease: Diversity, Tools and Therapeutic Targets.

    J Mol Neurosci. 2016 Nov;60(3):390-404

    Authors: Grubman A, Kanninen KM, Malm T

    Abstract
    Given the importance of microglia to inflammatory, phagocytic and synaptic modulatory processes, their function is vital in physiological and pathological brain. The impairment of microglia in Alzheimer's disease has been demonstrated on genetic, epigenetic, transcriptional and functional levels using unbiased systems level approaches. Recent studies have highlighted the immense phenotypic diversity of microglia, including the ability to adopt distinct and dynamic phenotypes in ageing and disease. We review the origins and functions of healthy microglia and the established and emerging models and techniques available for their study. Furthermore, we highlight recent advances on the role, heterogeneity and dysfunction of microglia in Alzheimer's disease and discuss the potential for therapeutic interventions targeting microglia. Microglia-selective molecular fingerprints will guide detailed functional analysis of microglial subsets and may aid in the development of therapies specifically targeting microglia.

    PMID: 27660215 [PubMed - indexed for MEDLINE]

pubmed: alzheimer's and stem...
NCBI: db=pubmed; Term=alzheimer's and stem cell treatment
NCBI pubmed
  • Aberrant iPSC-derived human astrocytes in Alzheimer's disease.
    Related Articles

    Aberrant iPSC-derived human astrocytes in Alzheimer's disease.

    Cell Death Dis. 2017 Mar 23;8(3):e2696

    Authors: Jones VC, Atkinson-Dell R, Verkhratsky A, Mohamet L

    Abstract
    The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs). All astrocytes expressed functional markers including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter-1 (EAAT1), S100B and glutamine synthetase (GS) comparable to that of adult astrocytes in vivo. However, induced astrocytes derived from both SAD and FAD patients exhibit a pronounced pathological phenotype, with a significantly less complex morphological appearance, overall atrophic profiles and abnormal localisation of key functional astroglial markers. Furthermore, NPCs derived from identical patients did not show any differences, therefore, validating that remodelled astroglia are not as a result of defective neural intermediates. This work not only presents a novel model to study the mechanisms of human astrocytes in vitro, but also provides an ideal platform for further interrogation of early astroglial cell autonomous events in AD and the possibility of identification of novel therapeutic targets for the treatment of AD.

    PMID: 28333144 [PubMed - in process]

  • Multitasking Microglia and Alzheimer's Disease: Diversity, Tools and Therapeutic Targets.
    Related Articles

    Multitasking Microglia and Alzheimer's Disease: Diversity, Tools and Therapeutic Targets.

    J Mol Neurosci. 2016 Nov;60(3):390-404

    Authors: Grubman A, Kanninen KM, Malm T

    Abstract
    Given the importance of microglia to inflammatory, phagocytic and synaptic modulatory processes, their function is vital in physiological and pathological brain. The impairment of microglia in Alzheimer's disease has been demonstrated on genetic, epigenetic, transcriptional and functional levels using unbiased systems level approaches. Recent studies have highlighted the immense phenotypic diversity of microglia, including the ability to adopt distinct and dynamic phenotypes in ageing and disease. We review the origins and functions of healthy microglia and the established and emerging models and techniques available for their study. Furthermore, we highlight recent advances on the role, heterogeneity and dysfunction of microglia in Alzheimer's disease and discuss the potential for therapeutic interventions targeting microglia. Microglia-selective molecular fingerprints will guide detailed functional analysis of microglial subsets and may aid in the development of therapies specifically targeting microglia.

    PMID: 27660215 [PubMed - indexed for MEDLINE]