Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 144, Issue 3, Pages 151-164Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2020.07.011
Keywords
Parkinson's disease; Glutamate-induced excitotoxicity; Inflammation; Astrocytes; Microglia
Categories
Funding
- UniPD
- Italian Ministry of Health [GR-201602363461]
- Department of Biology, UniPD
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Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamate transmission efficiency depends on the correct functionality and expression of a plethora of receptors and transporters, located both on neurons and glial cells. Of note, glutamate reuptake by dedicated transporters prevents its accumulation at the synapse as well as non-physiological spillover. Indeed, extracellular glutamate increase causes aberrant synaptic signaling leading to neuronal excitotoxicity and death. Moreover, extrasynaptic glutamate diffusion is strongly associated with glia reaction and neuroinflammation. Glutamate-induced excitotoxicity is mainly linked to an impaired ability of glial cells to reuptake and respond to glutamate, then this is considered a common hallmark in many neurodegenerative diseases, including Parkinson's disease (PD). In this review, we discuss the function of astrocytes and microglia in glutamate homeostasis, focusing on how glial dysfunction causes glutamate-induced excitotoxicity leading to neurodegeneration in PD. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
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