Aberrant iPSC-derived human astrocytes in Alzheimer's disease

Jones, Vicky Claire; Atkinson-Dell, Rebecca; Verkhratsky, Alexei; Mohamet, Lisa

doi:10.1038/cddis.2017.89

Cited by 150 publications

(143 citation statements)

References 48 publications

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“…Table shows some features of aberrant glial cells, including astrocytes or microglia, abnormally‐expressing markers from different cell lineages have been also reported in Alzheimer's disease, Huntington's disease, central nervous system acute lesions and aging, as well as glioma, brain ischemia and trauma, further suggesting the phenotypic switch is strongly associated with inflammation and tissue remodeling after damage.…”

Section: Phenotypic Heterogeneity Of Astrocytes In Als and Other Neurmentioning

confidence: 80%

Phenotypic heterogeneity of astrocytes in motor neuron disease

Trías

Barbeito

Yamanaka

2018

Clinical & Exp Neuroim

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Accumulating evidence has shown that astrocytes do not just support the function of neurons, but play key roles in maintaining the brain environment in health and disease. Contrary to the traditional understanding of astrocytes as static cells, reactive astrocytes possess more diverse functions and phenotypes than previously predicted. In the present focused review, we summarize the evidence showing that astrocytes are playing profound roles in the disease process of amyotrophic lateral sclerosis. Aberrantly activated astrocytes in amyotrophic lateral sclerosis rodents express microglial molecular markers and provoke toxicities to accelerate disease progression. In addition, TIR domain–containing adapter protein–inducing interferon‐β‐dependent innate immune pathway in astrocytes also has a novel function in terminating glial activation and neuroinflammation. Furthermore, heterogeneity in phenotypes and functions of astrocytes are also observed in various disease conditions, such as other neurodegenerative diseases, ischemia, aging and acute lesions in the central nervous system. Through accumulating knowledge of the phenotypic and functional diversity of astrocytes, these cells will become more attractive therapeutic targets for neurological diseases.

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Section: Phenotypic Heterogeneity Of Astrocytes In Als and Other Neurmentioning

confidence: 80%

Phenotypic heterogeneity of astrocytes in motor neuron disease

Trías

Barbeito

Yamanaka

2018

Clinical & Exp Neuroim

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“…Astrocytes associated with senile plaques display Ca 21 hyperexcitability and generate abnormal propagating intercellular Ca 21 waves. (104,118,129,170,201,202,204,261,264,267,273) Ageing-related tau astrogliopathy Exclusive expression of pathological tau in astrocytes is the sole histological symptom of several age-dependent dementias.…”

Section: Nosological Forms Astrocytopathy Referencesmentioning

confidence: 99%

Stratification of astrocytes in healthy and diseased brain

2017

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Astrocytes, a subtype of glial cells, come in variety of forms and functions. However, overarching role of these cell is in the homeostasis of the brain, be that regulation of ions, neurotransmitters, metabolism or neuronal synaptic networks. Loss of homeostasis represents the underlying cause of all brain disorders. Thus, astrocytes are likely involved in most if not all of the brain pathologies. We tabulate astroglial homeostatic functions along with pathological condition that arise from dysfunction of these glial cells. Classification of astrocytes is presented with the emphasis on evolutionary trails, morphological appearance and numerical preponderance. We note that even though, astrocytes from a variety of mammalian species share some common featured, human astrocytes appear to be the largest and most complex of all astrocytes studied thus far. It is then an imperative to develop humanized models to study the role of astrocytes in brain pathologies, which is perhaps most abundantly clear in the case of glioblastoma multiforme.

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“…Very recently, AD-associated astrocyte dysfunction has also been described in human iPSC-derived cell models. Using this model, atrophy of astrocytes and abnormal expression of astrocytic markers were demonstrated in iPSC-derived astrocytes from patients with familial and sporadic forms of AD [54]. We have also shown that iPSC-derived AD astrocytes are compromised in neuronal supportive function, and display increased β-amyloid production and oxidative stress, altered cytokine release, and dysregulated Ca2+ homeostasis [67].…”

Section: Astrocytes In Alzheimer's Diseasementioning

confidence: 83%

“…In addition to rodent models, recent advances in stem cell technologies have promoted the use of human-based cell models for AD research. For example, it is now possible to model AD in vitro by using induced pluripotent stem cells (iPSCs) and cells derived from these by differentiation [53][54][55].…”

Section: Astrocytes In Alzheimer's Diseasementioning

confidence: 99%

Mitochondrial Function in Alzheimer’s Disease: Focus on Astrocytes

Lampinen¹,

Belaya²,

Boccuni³

et al. 2018

Astrocyte - Physiology and Pathology

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The brain is one of the most energy-requiring organs in the human body. Mitochondria not only generate this energy, but are centrally involved critical cellular functions including maintenance of calcium homeostasis, synthesis of biomolecules, and cell signaling. Even though neurons and astrocytes preferentially use different energy substrates and metabolic pathways, these two cell types are intricately linked in their energy metabolism. Recently it has become clear that astrocytes have a key role in the regulation and support of the neuronal mitochondrial quality control, yet several questions remain unanswered to fully understand the mechanisms of mitochondrial function, transport, turnover and degradation in astrocytes. Alzheimer's disease is the most common neurodegenerative disorder, the exact mechanisms of which remain incompletely understood. The fact that astrocytic mitochondrial dysfunction is an early event in the pathogenesis of Alzheimer's disease suggests that more research on mitochondrial function and impairment is required in the hopes of disease alleviation in the future.

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Aberrant iPSC-derived human astrocytes in Alzheimer's disease

Cited by 150 publications

References 48 publications

Phenotypic heterogeneity of astrocytes in motor neuron disease

Phenotypic heterogeneity of astrocytes in motor neuron disease

Stratification of astrocytes in healthy and diseased brain

Mitochondrial Function in Alzheimer’s Disease: Focus on Astrocytes

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