Glutamate and glutamine metabolism in neurodegenerative diseases

Glutamate is known as the most important excitatory neurotransmitter in brain. Glutamate and glutamine recycling is very essential to maintain the nitrogen metabolism. Despite of its major functions, its dysregulation is a basic pathology which is common to neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS). Amyloid-β and Tau in AD disrupt glutamate uptake and the glutamate-glutamine cycle, accelerating synaptic failure, whereas loss of astrocytic EAAT2 in ALS generates unrelenting excitotoxicity and motor neuron demise. Toxic α-synuclein aggregation in PD exacerbates dopamine-glutamate imbalance through destabilizing corticostriatal transmission. This review explores on the key mechanisms by which glutamate impairment leads to the pathogenies of neurogenerative disorders and also about current medications like amantadine, memantine, and riluzole which are glutamate antagonists, are shown to partially alleviative but cannot halt the advancement of the disease. One of the potential targets for disease-modifying treatments could be the receptor modulation, astrocytic function, and elimination of excess glutamate.