Glutamate, glutamate transporters, and circadian rhythm sleep disorders in neurodegenerative diseases.

Glutamate, a primary excitatory neurotransmitter as well as an important intermediate of the cellular metabolism in the brain, has a widespread influence in the sleep-wake regulatory system. Glutamate transporters, including vesicular glutamate transporters and excitatory amino acid transporters, serve as the main force to control the extracellular concentration of glutamate in the brain. They are likely to be critical tools needed for the brain to modulate the sleep-wake cycle, and likely innervated by the circadian rhythm system in a day-night variant pattern either. Since nearly all patients with neurodegenerative diseases suffer rhythmic sleep disorders in the initial stages, which become aggravated with the development of disease and often exhibit glutamate uptake dysfunction either, we consider whether the glutamate transporters of both types could be used as the potential targets to help redress the circadian rhythm sleep disorders of patients with neurodegenerative diseases. Therefore, in this review, we sought to analyze the principles governing glutamate transmission and discuss whether the circadian rhythm regulatory properties of these processes endow glutamate transporters with unique functions in the sleep-wake shift of the brain. We attempt to provide a theoretical framework in this field for future studies, and to help in the exploration of potential therapeutic targets to delay or prevent the development of neurodegenerative diseases.