Internal medicine

Neuroscience

Receptor

Serotonin

Disease

Excitotoxicity

Biology

Neuroinflammation

Reuptake

Chemistry

Immunology

Inflammation

Neurodegeneration

Microglia

Metabotropic glutamate receptor

Metabotropic glutamate receptor 6

NMDA receptor

Cell biology

Biochemistry

Glutamate receptor

Medicine

Journal of Pharmacological Sciences

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.

Glutamate-induced excitotoxicity in Parkinson's disease: The role of glial cells