Glia–neuron interactions in neurological diseases: Testing non-cell autonomy in a dish

Meyer, Kathrin; Kaspar, Brian K.

doi:10.1016/j.brainres.2015.12.051

Cited by 36 publications

(24 citation statements)

References 216 publications

(159 reference statements)

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“…A number of coculture platforms have been developed for the study of neurological disease, shedding light on the interactions that occur between neural cell types (excellently reviewed by Meyer and Kaspar, 2017 ). These vary in their design and complexity, from focusing on paracrine signaling through transwell interactions to culturing disparate cell populations in pre-determined orientations to modeling physiological structures such as the blood brain barrier.…”

Section: The Future Of Hipsc-based Drug Screeningmentioning

confidence: 99%

The Importance of Non-neuronal Cell Types in hiPSC-Based Disease Modeling and Drug Screening

Gonzalez

Gregory

Brennand

2017

Front. Cell Dev. Biol.

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Current applications of human induced pluripotent stem cell (hiPSC) technologies in patient-specific models of neurodegenerative and neuropsychiatric disorders tend to focus on neuronal phenotypes. Here, we review recent efforts toward advancing hiPSCs toward non-neuronal cell types of the central nervous system (CNS) and highlight their potential use for the development of more complex in vitro models of neurodevelopment and disease. We present evidence from previous works in both rodents and humans of the importance of these cell types (oligodendrocytes, microglia, astrocytes) in neurological disease and highlight new hiPSC-based models that have sought to explore these relationships in vitro. Lastly, we summarize efforts toward conducting high-throughput screening experiments with hiPSCs and propose methods by which new screening platforms could be designed to better capture complex relationships between neural cell populations in health and disease.

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Section: The Future Of Hipsc-based Drug Screeningmentioning

confidence: 99%

The Importance of Non-neuronal Cell Types in hiPSC-Based Disease Modeling and Drug Screening

Gonzalez

Gregory

Brennand

2017

Front. Cell Dev. Biol.

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“…Screenings can be aimed to identify compounds that modify a particular aspect of astrocyte biology (e.g. oxidative stress) [198] or to identify candidates that revert astrocyte-mediated motor neuron toxicity in ALS [199]. However, implementation of effective drug treatments in ALS may be challenging in view of the changes in the ATP-binding cassette (ABC) transporters observed in the disease.…”

Section: Therapeutic Potential Of Astrocytesmentioning

confidence: 99%

Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis

Pehar

Harlan

Killoy

et al. 2018

CPD

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Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. The molecular mechanism underlying the progressive degeneration of motor neuron remains uncertain but involves a non-cell autonomous process. In acute injury or degenerative diseases astrocytes adopt a reactive phenotype known as astrogliosis. Astrogliosis is a complex remodeling of astrocyte biology and most likely represents a continuum of potential phenotypes that affect neuronal function and survival in an injury-specific manner. In ALS patients, reactive astrocytes surround both upper and lower degenerating motor neurons and play a key role in the pathology. It has become clear that astrocytes play a major role in ALS pathology. Through loss of normal function or acquired new characteristics, astrocytes are able to influence motor neuron fate and the progression of the disease. The use of different cell culture models indicates that ALS-astrocytes are able to induce motor neuron death by secreting a soluble factor(s). Here, we discuss several pathogenic mechanisms that have been proposed to explain astrocyte-mediated motor neuron death in ALS. In addition, examples of strategies that revert astrocyte-mediated motor neuron toxicity are reviewed to illustrate the therapeutic potential of astrocytes in ALS. Due to the central role played by astrocytes in ALS pathology, therapies aimed at modulating astrocyte biology may contribute to the development of integral therapeutic approaches to halt ALS progression.

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“…The emerging line of evidence has shed light on the importance of glia in their bidirectional communication with neurons, their adaptability in various pathologies, modulation of neuronal activity, and phenotypic changes in response to neuronal injury (Benarroch, 2005;von Bernhardi et al, 2016). Throughout the brain tissue, neurons are closely associated with glial cells including astrocytes, oligodendrocytes, and microglia and their dynamic interactions are important for normal brain function (Chung et al, 2015;Meyer and Kaspar, 2017). It has been speculated that every type of neurological disease involves a glial component, which may be a primary or secondary cause (Kaminsky et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Afridi

Kim

Rahman

et al. 2020

Front. Cell. Neurosci.

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Glial cells are multifunctional, non-neuronal components of the central nervous system with diverse phenotypes that have gained much attention for their close involvement in neuroinflammation and neurodegenerative diseases. Glial phenotypes are primarily characterized by their structural and functional changes in response to various stimuli, which can be either neuroprotective or neurotoxic. The reliance of neurons on glial cells is essential to fulfill the energy demands of the brain for its proper functioning. Moreover, the glial cells perform distinct functions to regulate their own metabolic activities, as well as work in close conjunction with neurons through various secreted signaling or guidance molecules, thereby constituting a complex network of neuron-glial interactions in health and disease. The emerging evidence suggests that, in disease conditions, the metabolic alterations in the glial cells can induce structural and functional changes together with neuronal dysfunction indicating the importance of neuron-glia interactions in the pathophysiology of neurological disorders. This review covers the recent developments that implicate the regulation of glial phenotypic changes and its consequences on neuron-glia interactions in neurological disorders. Finally, we discuss the possibilities and challenges of targeting glial metabolism as a strategy to treat neurological disorders.

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Glia–neuron interactions in neurological diseases: Testing non-cell autonomy in a dish

Cited by 36 publications

References 216 publications

The Importance of Non-neuronal Cell Types in hiPSC-Based Disease Modeling and Drug Screening

The Importance of Non-neuronal Cell Types in hiPSC-Based Disease Modeling and Drug Screening

Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

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