2024
Metabolic 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
2023
S-Nitrosylation-mediated dysfunction of TCA cycle enzymes in synucleinopathy studied in postmortem human brains and hiPSC-derived neurons
Doulias P, Yang H, Andreyev A, Dolatabadi N, Scott H, K Raspur C, Patel P, Nakamura T, Tannenbaum S, Ischiropoulos H, Lipton S. S-Nitrosylation-mediated dysfunction of TCA cycle enzymes in synucleinopathy studied in postmortem human brains and hiPSC-derived neurons. Cell Chemical Biology 2023, 30: 965-975.e6. PMID: 37478858, PMCID: PMC10530441, DOI: 10.1016/j.chembiol.2023.06.018.Peer-Reviewed Original ResearchConceptsTCA cycleLewy body dementiaAberrant S-nitrosylationMitochondrial metabolic dysfunctionTricarboxylic acid cyclePluripotent stem cellsMitochondrial energy metabolismParkinson's diseaseHiPSC-derived neuronsTCA enzymesMetabolic flux experimentsS-nitrosylationAcid cycleCell deathNeuronal cell deathΑ-ketoglutaratePostmortem human brainEnergy metabolismStem cellsLBD brainsDendritic lengthBioenergetic failureMetabolic dysfunctionSynaptic integrityPathophysiological relevance