Mechanisms of Neuronal Apoptosis and Excitotoxicity

Neurons are postmitotic cells that may remain functional for years and cannot be replaced easily, so irreversible neuronal damage could result in destructive diseases like neurodegenerative illnesses. The mechanism of neuronal cell death represents a fundamental factor in determining the pathway of many diseases, and since the neurons take a long time to be lost, it might be challenging to recognize the modes of cell death and the initiating events. Neurological studies have become more interested recently in the molecular mechanisms of apoptotic and excitotoxic cell death in the central nervous system lesions and their relevance to different neurodegenerative disorders. As well, the interaction between apoptosis and excitotoxicity has drawn attention to shed light on the postulation that excitotoxic cell death pathways could be mediated by apoptotic processes. Numerous findings demonstrate increased extracellular concentrations of glutamate neurotransmitters and overstimulation of postsynaptic glutamate receptors in most neurodegenerative diseases. The resultant excitotoxic response is likely to elicit some cytotoxic events including increased calcium overload, accumulation of reactive oxygen species, mitochondrial dysfunction, endoplasmic reticulum stress, deficiency in energy supply, and DNA damage, which result in the induction of neuronal death pathways mostly by apoptosis, autophagy, necrosis, or by a combination of different death modes depending on different factors like the insult severity and duration. Evidence of the crucial role of the apoptotic-excitotoxic pathway in neurodegenerative illnesses is growing, although additional research into the underlying mechanism by which it contributes to neurodegeneration is still needed.