2022
Inhibition of autophagic flux by S-nitrosylation of SQSTM1/p62 promotes neuronal secretion and cell-to-cell transmission of SNCA/α-synuclein in Parkinson disease and Lewy body dementia
Oh C, Nakamura T, Lipton S. Inhibition of autophagic flux by S-nitrosylation of SQSTM1/p62 promotes neuronal secretion and cell-to-cell transmission of SNCA/α-synuclein in Parkinson disease and Lewy body dementia. Autophagy Reports 2022, 1: 223-225. PMID: 38098743, PMCID: PMC10721282, DOI: 10.1080/27694127.2022.2076770.Peer-Reviewed Original ResearchLewy body dementiaParkinson's diseaseSNCA/α-synucleinAutophagic fluxNitric oxideΑ-synucleinHuman postmortem brainS-nitrosylationNeuronal damageAberrant protein S-nitrosylationSynaptic damageΑ-synucleinopathiesPostmortem brainsPathogenic eventsDiseased brainExcessive reactive oxygenSQSTM1/p62Neurodegenerative disordersInhibits autophagic fluxNeuronal secretionCell-based modelCell transmissionProtein S-nitrosylationDementiaDisease
2021
S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD
Pirie E, Oh C, Zhang X, Han X, Cieplak P, Scott H, Deal A, Ghatak S, Martinez F, Yeo G, Yates J, Nakamura T, Lipton S. S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2021368118. PMID: 33692125, PMCID: PMC7980404, DOI: 10.1073/pnas.2021368118.Peer-Reviewed Original ResearchConceptsProtein misfolding/aggregationCell spreadMisfolding/aggregationRNA-binding activityOligomerization/aggregationHuman-induced pluripotent stem cellsProtein TDP-43Pluripotent stem cellsALS/FTDTDP-43 aggregationTDP-43Cognate proteinProtein aggregationS-nitrosylationRare genetic mutationsCell-based modelFTD disordersAmyotrophic lateral sclerosisAbsence of mutationsTriggers aggregationStem cellsGenetic mutationsDisulfide linkagesNitrosative stressNeurodegenerative disorders