ArticleCell chemical biology2023
S-Nitrosylation-mediated dysfunction of TCA cycle enzymes in synucleinopathy studied in postmortem human brains and hiPSC-derived neurons.
Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Aberrant protein S-nitrosylation disrupts axonal development and metabolic homeostasis in a Cntnap2 mouse model of autism.Redox biology · 2026Article
- Proteome-wide profiling of S-nitrosylated proteins using the SNOTRAP probe and mass spectrometry-based detection.Nature protocols · 2026Review
- Metabolic modulation of TCA cycle bySynthetic and systems biotechnology · 2026Article
- Synaptic rescue in an Alzheimer's mouse model: low-temperature steam-derived black ginseng oligosaccharides remodel protein S-nitrosylation-NADPH oxidase axis.NPJ science of food · 2026Article
- Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review.Current issues in molecular biology · 2026Review
- Aberrant Protein S-Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases.Journal of neurochemistry · 2026Review
- Inhibition of hepatic gluconeogenesis in type 2 diabetes by metformin: complementary role of nitric oxide.Medical gas research · 2025Review
- Aberrant S-nitrosylation in the TCA cycle contributes to mitochondrial dysfunction, energy compromise, and synapse loss in neurodegenerative diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Redox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Mitochondrial dysfunction-mediated metabolic remodeling of TCA cycle promotes Parkinson's disease through inhibition of H3K4me3 demethylation.Cell death discovery · 2025Article
- Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism.Aging and disease · 2025Review
- Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer's and related dementias.Neuron · 2024Review
- Single-Cell Patch-Clamp/Proteomics of Human Alzheimer's Disease iPSC-Derived Excitatory Neurons Versus Isogenic Wild-Type Controls Suggests Novel Causation and Therapeutic Targets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The chemical biology of dinitrogen trioxide.Redox biochemistry and chemistry · 2024Article
- Metabolic Bypass Rescues Aberrant S-nitrosylation-Induced TCA Cycle Inhibition and Synapse Loss in Alzheimer's Disease Human Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
A causal relationship between mitochondrial metabolic dysfunction and neurodegeneration has been implicated in synucleinopathies, including Parkinson disease (PD) and Lewy body dementia (LBD), but underlying mechanisms are not fully understood. Here, using human induced pluripotent stem cell (hiPSC)-derived neurons with mutation in the gene encoding α-synuclein (αSyn), we report the presence of aberrantly S-nitrosylated proteins, including tricarboxylic acid (TCA) cycle enzymes, resulting in activity inhibition assessed by carbon-labeled metabolic flux experiments. This inhibition principally affects α-ketoglutarate dehydrogenase/succinyl coenzyme-A synthetase, metabolizing α-ketoglutarate to succinate. Notably, human LBD brain manifests a similar pattern of aberrantly S-nitrosylated TCA enzymes, indicating the pathophysiological relevance of these results. Inhibition of mitochondrial energy metabolism in neurons is known to compromise dendritic length and synaptic integrity, eventually leading to neuronal cell death. Our evidence indicates that aberrant S-nitrosylation of TCA cycle enzymes contributes to this bioenergetic failure.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.