GluN2B of NMDA Receptor and Calmodulin: Balanced Calcium Regulation to Combat Alzheimer's Disease

Abstract: N-methyl-D-Aspartate receptor (NMDAR) mediated excitatory glutamatergic neurotransmission is essential for synaptic plasticity and neuronal survival. However, excessive NMDAR activation results in excitotoxicity and encourages cell death, as well as providing a probable explanation for the development of Alzheimer';s disease (AD) like pathology. It's possible because of Mg2+ ions, which block NMDA receptors while at rest and are unable to do so under synaptic plasticity. Earlier studies have reported that blocking NMDAR by Mg2+ can improve AD. Further, calcium homeostasis can be another convincing explanation for AD. Thereby, calcium plays an etiological factor in synaptic plasticity and can cause Alzheimer';s disease. According to studies, calcium homeostasis is maintained by calmodulin, however, calcium imbalance because of calmodulin can result in excitotoxicity. Additionally, the endoplasmic reticulum can disturb the body';s calcium homeostasis by malfunctioning mitochondria. An attempt has been made to review the different subunits of NMDA receptors, Calmodulin and Mitochondrial calcium release and their physiological roles to understand the possible aetiology for the mitigation of AD.