Mitochondria1AstrocyteEndoplasmic reticulum (ER)DNA damageMitochondrial dysfunctionATP depletionFall in mitochondrial membrane potentialLow Ca2+ buffering capacityReduced expressionMitochondriatBidElevated glutamatelevelsAggregatesIncreased expressionNeurofilament damageIncreased ROSAbnormal Rab5 dependent endycytosis?AggregatesImpairment of axonal transportp38TNFalphaMKK6ApoptosisO2-ASK1MAPK Signaling PathwayGPX1CATNEFMH2O2CYTCNEFHMKK3NOS1NOPPP3CADNACup53 Signaling PathwayCCSNOReactive Oxygen Species (ROS)DAXXOHCa2+NEFLProteasomePRPHH2ORAC1RAB5APPP3CCsynaptic transmission, glutamatergicALS2PPP3CBPresynaptic neuronMicroglial cellMotor neuronNOL-ArginineONOO-EAAT2L-Glutamic acidL-Glutamic acidP53Neuron deathAPAF1CASP3CASP9ActivationL-Glutamic acidIncrease incytosolic Ca2+Ca2+Derlin-1Accumulation ofmisfolded proteinsER stressDisturbance ofmitochondrial respirationCASP1BIDSOD1TOM40BCL2BCL2L1BAXBADUbiquitin proteosomedysfunctionCASP12TNFalphaTNFRGRIA1NONOSOD1ActivationCa2+ASK1ApoptosisReactive Oxygen Species (ROS)SOD1SOD1