MitochondriaAstrocyteEndoplasmic reticulum (ER)DNA damageShould this be calcineurin complex or protein phosphatase 3, regulatory subunit?Elevated glutamatelevelsAggregatesMKK3CYTCReactive Oxygen Species (ROS)NEFMNEFLNOS1NOASK1DAXXMKK6DNACa2+NOp38TNFalphaMAPK Signaling PathwayNEFHPresynaptic neuronMicroglial cellMotor neuronNOL-ArginineONOO-EAAT2L-Glutamic acidL-Glutamic acidP53p53 signalingpathwayNeuron deathAPAF1CASP3CASP9ApoptosisActivationcalcineurin complexL-Glutamic acidsynaptic transmission, glutamatergicIncrease incytosolic Ca2+Ca2+DERL1_HUMANAccumulation ofmisfolded proteinsER stressATP depletionFall in mitochondrialmembrane potentialIncreased ROSDisturbance ofmitochondrial respirationMitochondrialdysfunctionLow Ca2+ bufferingcapacityCa2+CASP1BID_HUMANSOD1TOM40_HUMANBIM-BCL-2 complexBIM-BCL-xl complexBAXBADproteasome complexUbiquitin proteosomedysfunctionApoptosisCASP12MAP3K5TNFalphaTNFRGRIA1NONOSOD1