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Astrocyte dysfunction in neurological disorders: a molecular perspective

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TLDR
An improved understanding of astrocyte biology and heterogeneity and the involvement of these cells in pathogenesis offers the potential for developing novel strategies to treat neurological disorders.
Abstract
Recent work on glial cell physiology has revealed that glial cells, and astrocytes in particular, are much more actively involved in brain information processing than previously thought. This finding has stimulated the view that the active brain should no longer be regarded solely as a network of neuronal contacts, but instead as a circuit of integrated, interactive neurons and glial cells. Consequently, glial cells could also have as yet unexpected roles in the diseased brain. An improved understanding of astrocyte biology and heterogeneity and the involvement of these cells in pathogenesis offers the potential for developing novel strategies to treat neurological disorders.

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Journal ArticleDOI

Astrocytes: biology and pathology

TL;DR: Astrocyte functions in healthy CNS, mechanisms and functions of reactive astrogliosis and glial scar formation, and ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions are reviewed.
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Molecular dissection of reactive astrogliosis and glial scar formation.

TL;DR: Developments in the signaling mechanisms that regulate specific aspects of reactive astrogliosis are reviewed and the potential to identify novel therapeutic molecular targets for diverse neurological disorders is highlighted.
Journal ArticleDOI

Air pollution: mechanisms of neuroinflammation and CNS disease

TL;DR: Recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease are summarized.
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The tripartite synapse: roles for gliotransmission in health and disease

TL;DR: In this article, targeted molecular genetic approaches that have demonstrated that alterations in protein expression in astrocytes can lead to serious changes in neuronal function were discussed, and the concept of "astrocyte activation spectrum" was introduced, in which enhanced and reduced gliotransmission might contribute to epilepsy and schizophrenia.
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Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury

TL;DR: The neurological consequences of TBI are reviewed, focusing on the long-term complications of such injuries, and potential mechanisms linking vascular pathology to neuronal dysfunction and degeneration are analyzed.
References
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Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis

TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
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Knockout of Glutamate Transporters Reveals a Major Role for Astroglial Transport in Excitotoxicity and Clearance of Glutamate

TL;DR: It is suggested that glial glutamate transporters provide the majority of functional glutamate transport and are essential for maintaining low extracellular glutamate and for preventing chronic glutamate neurotoxicity.
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Epilepsy and Exacerbation of Brain Injury in Mice Lacking the Glutamate Transporter GLT-1

TL;DR: Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury, which can be attributed to elevated levels of residual glutamate in the brains of these mice.
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Glutamate-mediated astrocyte-neuron signalling.

TL;DR: Astrocytes regulate neuronal calcium levels through the calcium-dependent release of glutamate, and an NMDA (N-methyl-d-aspartate) receptor-mediated increase in neuronal calcium is demonstrated.
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Astrocytes, from brain glue to communication elements: the revolution continues.

TL;DR: The recent recognition that astrocytes are organized in separate territories and possess active properties — notably a competence for the regulated release of 'gliotransmitters', including glutamate — has enabled us to develop an understanding of previously unknown functions for astroCytes.
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