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Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders

期刊

CELLS
卷 11, 期 7, 页码 -

出版社

MDPI
DOI: 10.3390/cells11071139

关键词

astrocyte; glutamate; neurodegenerative diseases; V-ATPases; calcium; exocytosis; cystine; glutamate antiporter; Bestrophin-1; hemichannels

资金

  1. Manipal Academy of Higher Education
  2. Manipal Academy of Higher Education [MAHE/DREG/PhD/IMF/2019]

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This article reviews the different mechanisms of astrocytic glutamate release and their implications in neurodegenerative diseases. Regulating astrocytic glutamatergic transmission could provide new approaches for the treatment of these diseases.
Several neurodegenerative disorders involve impaired neurotransmission, and glutamatergic neurotransmission sets a prototypical example. Glutamate is a predominant excitatory neurotransmitter where the astrocytes play a pivotal role in maintaining the extracellular levels through release and uptake mechanisms. Astrocytes modulate calcium-mediated excitability and release several neurotransmitters and neuromodulators, including glutamate, and significantly modulate neurotransmission. Accumulating evidence supports the concept of excitotoxicity caused by astrocytic glutamatergic release in pathological conditions. Thus, the current review highlights different vesicular and non-vesicular mechanisms of astrocytic glutamate release and their implication in neurodegenerative diseases. As in presynaptic neurons, the vesicular release of astrocytic glutamate is also primarily meditated by calcium-mediated exocytosis. V-ATPase is crucial in the acidification and maintenance of the gradient that facilitates the vesicular storage of glutamate. Along with these, several other components, such as cystine/glutamate antiporter, hemichannels, BEST-1, TREK-1, purinergic receptors and so forth, also contribute to glutamate release under physiological and pathological conditions. Events of hampered glutamate uptake could promote inflamed astrocytes to trigger repetitive release of glutamate. This could be favorable towards the development and worsening of neurodegenerative diseases. Therefore, across neurodegenerative diseases, we review the relations between defective glutamatergic signaling and astrocytic vesicular and non-vesicular events in glutamate homeostasis. The optimum regulation of astrocytic glutamatergic transmission could pave the way for the management of these diseases and add to their therapeutic value.

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