ArticleActa neuropathologica communications2018
Activity of translation regulator eukaryotic elongation factor-2 kinase is increased in Parkinson disease brain and its inhibition reduces alpha synuclein toxicity.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 71 citations in OpenAlex.
- Betulinaldehyde Ameliorates Aβ-Induced Neurotoxicity and Cognitive Deficits by Modulating the eEF2K/eEF2 Pathway.CNS neuroscience & therapeutics · 2026Article
- Multilayer Proteome and Metabolome-Based Validation Uncovers Combined Regulatory Roles and Predictive Values of 6 RNA Modifications and Cellular Senescence in Alzheimer's Disease.CNS neuroscience & therapeutics · 2026Article
- Overactive Neuronal eEF2K/eEF2 signaling is associated with cognitive impairment and apathy-like behavior.Molecular psychiatry · 2026Article
- Spatial transcriptomics reveals the molecular signatures of prodromal and advanced α-synucleinopathy.iScience · 2026Article
- SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids.NPJ Parkinson's disease · 2026Article
- Deep Hypothermic Low Flow Results in Multiple Aspects of Neurological Deficits in Mice by eEF2 Hyperphosphorylation.Molecular neurobiology · 2025Article
- Hsa_Circ_0105596/FTO inhibits progression of Parkinson's disease by sponging miR-187-3p and regulating eEF2.Heliyon · 2024Article
- Advances in siRNA Drug Delivery Strategies for Targeted TNBC Therapy.Bioengineering (Basel, Switzerland) · 2024Review
- Application of Human Brain Organoids-Opportunities and Challenges in Modeling Human Brain Development and Neurodevelopmental Diseases.International journal of molecular sciences · 2023Review
- A beginner's guide into curated analyses of open access datasets for biomarker discovery in neurodegeneration.Scientific data · 2023Article
- Structure of the complex between calmodulin and a functional construct of eukaryotic elongation factor 2 kinase bound to an ATP-competitive inhibitor.The Journal of biological chemistry · 2023Article
- ADP enhances the allosteric activation of eukaryotic elongation factor 2 kinase by calmodulin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dysregulated proteostasis network in neuronal diseases.Frontiers in cell and developmental biology · 2023Review
- Article
- eEF2 in the prefrontal cortex promotes excitatory synaptic transmission and social novelty behavior.EMBO reports · 2022Article
- Maintenance of tRNA and elongation factors supports T3SS proteins translational elongations in pathogenic bacteria during nutrient starvation.Cell & bioscience · 2022Article
- Structural basis for the calmodulin-mediated activation of eukaryotic elongation factor 2 kinase.Science advances · 2022Article
- Review
- Article
- Angiotensin-(1-7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson's disease.Neural regeneration research · 2022Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Parkinson disease (PD) is the second most common neurodegenerative disorder and the leading neurodegenerative cause of motor disability. Pathologic accumulation of aggregated alpha synuclein (AS) protein in brain, and imbalance in the nigrostriatal system due to the loss of dopaminergic neurons in the substantia nigra- pars compacta, are hallmark features in PD. AS aggregation and propagation are considered to trigger neurotoxic mechanisms in PD, including mitochondrial deficits and oxidative stress. The eukaryotic elongation factor-2 kinase (eEF2K) mediates critical regulation of dendritic mRNA translation and is a crucial molecule in diverse forms of synaptic plasticity. Here we show that eEF2K activity, assessed by immuonohistochemical detection of eEF2 phosphorylation on serine residue 56, is increased in postmortem PD midbrain and hippocampus. Induction of aggressive, AS-related motor phenotypes in a transgenic PD M83 mouse model also increased brain eEF2K expression and activity. In cultures of dopaminergic N2A cells, overexpression of wild-type human AS or the A53T mutant increased eEF2K activity. eEF2K inhibition prevented the cytotoxicity associated with AS overexpression in N2A cells by improving mitochondrial function and reduced oxidative stress. Furthermore, genetic deletion of the eEF2K ortholog efk-1 in C. elegans attenuated human A53T AS induced defects in behavioural assays reliant on dopaminergic neuron function. These data suggest a role for eEF2K activity in AS toxicity, and support eEF2K inhibition as a potential target in reducing AS-induced oxidative stress in PD.
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