Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer’s and related dementias
Oh C, Nakamura T, Zhang X, Lipton S. Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer’s and related dementias. Neuron 2024 PMID: 39515322, DOI: 10.1016/j.neuron.2024.10.013.Peer-Reviewed Original ResearchProtein S-nitrosylationS-nitrosylationEndoplasmic reticulumRedox-mediated posttranslational modificationDiseases associated with protein aggregationProtein aggregationSynapse lossModulating protein activityNetwork of proteinsMultiple neurodegenerative disordersUbiquitin-proteasome systemS-nitrosylation reactionPosttranslational modificationsMitochondrial metabolismExcessive nitrosative stressEnzymatic machineryRedox regulationProtein activityProtein networkDysfunction pathwayMicroglial phagocytosisSingle proteinsBioenergetic compromiseReview recent findingsProteinMetabolic Bypass Rescues Aberrant S‐nitrosylation‐Induced TCA Cycle Inhibition and Synapse Loss in Alzheimer's Disease Human Neurons
Andreyev A, Yang H, Doulias P, Dolatabadi N, Zhang X, Luevanos M, Blanco M, Baal C, Putra I, Nakamura T, Ischiropoulos H, Tannenbaum S, Lipton S. Metabolic Bypass Rescues Aberrant S‐nitrosylation‐Induced TCA Cycle Inhibition and Synapse Loss in Alzheimer's Disease Human Neurons. Advanced Science 2024, 11: 2306469. PMID: 38235614, PMCID: PMC10966553, DOI: 10.1002/advs.202306469.Peer-Reviewed Original ResearchTricarboxylic acidOxidative phosphorylationAlzheimer's diseaseSynapse lossSynaptic lossPathological correlate of cognitive declineHuman AD brainsTCA cycle inhibitionMetabolic flux experimentsAberrant S-nitrosylationPostmortem human AD brainIsogenic wild-typeAssociated with synaptic lossDysfunctional mitochondrial metabolismMitochondrial bioenergetic functionProtein S-nitrosylationModel of ADMitochondrial energy metabolismCell-permeable derivativeCorrelate of cognitive declineAD brainMitochondrial metabolismEnzyme functionHiPSC-based modelsBioenergetic function