When NNMT is suppressed, NAD+ levels rise
195,196,197 At the cellular level, this translates into a massive increase in cytoplasmic Na + concentration, membrane depolarisation and opening of voltage-gated Ca 2+ channels, which in turn promotes massive release of glutamate that results in even large depolarisation enlarging Na + and Ca 2+ influx thus completing the vicious circle of excitotoxic damage, as Ca 2+ overload triggers necrotic cell death
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