The study investigates the neurotoxic effects of homocysteine, a metabolite commonly elevated in conditions like homocystinuria and hyperhomocysteinemia. Homocysteine acts as both an agonist at the glutamate binding site of the N-methyl-D-aspartate (NMDA) receptor and a partial antagonist at the glycine coagonist site. Under physiological conditions, homocysteine's neurotoxic effects are minimal due to low glycine levels. However, under pathological conditions such as stroke or head trauma, where glycine levels are elevated, homocysteine's neurotoxicity becomes significant. The neurotoxicity is characterized by excessive Ca2+ influx and reactive oxygen species generation, leading to neuronal damage. The study also explores the potential mechanisms of homocysteine neurotoxicity, including its interaction with bicarbonate and disulfide cystine. These findings suggest that targeting NMDA receptors or downstream pathways may be therapeutic strategies for reducing homocysteine-induced neurotoxicity.The study investigates the neurotoxic effects of homocysteine, a metabolite commonly elevated in conditions like homocystinuria and hyperhomocysteinemia. Homocysteine acts as both an agonist at the glutamate binding site of the N-methyl-D-aspartate (NMDA) receptor and a partial antagonist at the glycine coagonist site. Under physiological conditions, homocysteine's neurotoxic effects are minimal due to low glycine levels. However, under pathological conditions such as stroke or head trauma, where glycine levels are elevated, homocysteine's neurotoxicity becomes significant. The neurotoxicity is characterized by excessive Ca2+ influx and reactive oxygen species generation, leading to neuronal damage. The study also explores the potential mechanisms of homocysteine neurotoxicity, including its interaction with bicarbonate and disulfide cystine. These findings suggest that targeting NMDA receptors or downstream pathways may be therapeutic strategies for reducing homocysteine-induced neurotoxicity.