Exploration of Neuroprotective Therapy

Table 2

Excitotoxic processes contributing to diseases of the central nervous system (CNS)

Disease	Excitotoxic process	References
Ischemia	Interruption of blood flow leading to energy failure Impairment of glutamate transport and NMDA receptors overactivation Sustained Ca²⁺ influx	[137, 138]
Epilepsy	Dysregulation of EAATs and increase in extracellular Glu levels	[139, 140]
Alzheimer’s disease	Amyloid-β_1-42 oligomers action on eNMDA receptors, leading to sustained Ca²⁺ influx, and mitochondrial and synaptic disfunction	[141, 142]
Alzheimer’s disease	Metabolic astrocytic dysfunction and inhibition of lactate production	[143, 144]
Amyotrophic lateral sclerosis	Upregulation of AMPA receptors Interneuron alterations and excitation-inhibition imbalance Downregulation of EAAT2 in astrocytes and altered astrocyte metabolism with release of toxic factors	[145, 146]
Parkinson’s disease	Loss of dopamine leading to dysregulation of Ca²⁺ homeostasis Overexpression of mGluR₅ receptors	[147, 148]
Huntington’s disease	Interaction between mutated HTT protein and the PSD-95 scaffold protein, leading to alteration of the Glu receptors and to impairment of glutamate signaling	[149]

NMDA: N-methyl-D-aspartate; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; EAATs: excitatory amino acid transporters