Role of mGlu receptors in psychiatric disorders – Recent advances

Pilc, Andrzej; Chaki, Shigeyuki

doi:10.1016/j.pbb.2023.173639

Cited by 1 publication

(1 citation statement)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The possibility to regulate glutamatergic transmission through mGluR modulation is attracting attention as well [ 196 , 197 ]. Unfortunately, to date, this approach is not yet producing particularly encouraging results, and some molecules targeting mGluRs have recently failed in clinical phases (as in the case of mGluR5 antagonists for ASD).…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Nicosia,

Giovenzana,

Misztak

et al. 2024

IJMS

View full text Add to dashboard Cite

Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory formation and consolidation as well as in fear and emotional processing, such as the hippocampus, prefrontal cortex, and amygdala, are predominantly glutamatergic. To ensure the physiological activity of the brain, glutamatergic transmission is finely tuned at synaptic sites. Disruption of the mechanisms responsible for glutamate homeostasis may result in the accumulation of excessive glutamate levels, which in turn leads to increased calcium levels, mitochondrial abnormalities, oxidative stress, and eventually cell atrophy and death. This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism in several diseases of the central nervous system, including neurodevelopmental, substance abuse, and psychiatric disorders. On the other hand, these disorders share neuroplasticity impairments in glutamatergic brain areas, which are accompanied by structural remodeling of glutamatergic neurons. In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions. Although clinical evidence is still limited and more studies are required, the regulation of glutamate homeostasis is attracting attention as a potential crucial target for the control of brain diseases.

show abstract

Section: Discussion and Future Perspectivesmentioning

confidence: 99%