The Role of Monosodium Glutamate (MSG) in Epilepsy and other Neurodegenerative Diseases: Phytochemical-based Therapeutic Approa-ches and Mechanisms

Epilepsy is a common neurological disease affecting 50 million individuals worldwide, and some forms of epilepsy do not respond to available treatments. Overactivation of the glutamate pathway and excessive entrance of calcium ions into neurons are proposed as the biochemical mechanisms behind epileptic seizures. However, the overactivation of neurons has also been associated with other neurodegenerative diseases (NDDs), such as Alzheimer's, Parkinson's, Huntington's, and multiple sclerosis. The most widely used food ingredient, monosodium glutamate (MSG), increases the level of free glutamate in the brain, putting humans at risk for NDDs and epilepsy. Glutamate is a key neurotransmitter that activates nerve cells. MSG acts on glutamate receptors, specifically NMDA and AMPA receptors, leading to an imbalance between excitatory glutamate and inhibitory GABA neurotransmission. This imbalance can cause hyperexcitability of neurons and lead to epileptic seizures. Overuse of MSG causes neuronal cells to become overexcited, which in turn leads to an increase in the flow of Ca²⁺ and Na⁺ ions, mutations, and upregulation in the enzymes superoxide dismutase 1 (SOD-1) and TDP43, all of which contribute to the development of NDDs. While TDP43 and SOD-1 protect cells from damage, a mutation in their genes makes the proteins unprotective and cause neurodegeneration. Yet to what extent mutant SOD1 and TDP43 aggregates contribute to neurotoxicity is generally unknown. This study is focused on neuroprotective herbal medications that can pass the blood-brain barrier and cure MSGinduced NDDs and the factors that influence MSG-induced glutaminergic, astrocyte, and GABAergic neuron abnormalities causing neurodegeneration.