ArticleBrain research2014
Excitotoxic glutamate insults block autophagic flux in hippocampal neurons.
Article in Brain research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Dysfunction of hippocampal cells and its role in cognitive impairment.Neural regeneration research · 2026Article
- Epilepsy and autophagy modulators: a therapeutic split.Autophagy · 2025Review
- Biased regulation of protein synthesis and hypoxic death by a conditional raptor mutation.Current biology : CB · 2025Article
- The Role of Autophagy in Excitotoxicity, Synaptic Mitochondrial Stress and Neurodegeneration.Autophagy reports · 2025Article
- Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator.Molecular medicine (Cambridge, Mass.) · 2023Review
- Quinolinic Acid Induces Alterations in Neuronal Subcellular Compartments, Blocks Autophagy Flux and Activates Necroptosis and Apoptosis in Rat Striatum.Molecular neurobiology · 2022Article
- A Review on Peripheral Tinnitus, Causes, and Treatments from the Perspective of Autophagy.Experimental neurobiology · 2022Review
- The dual roles of autophagy and the GPCRs-mediating autophagy signaling pathway after cerebral ischemic stroke.Molecular brain · 2022Review
- Calcium/Calmodulin-Dependent Protein Kinase II in Cerebrovascular Diseases.Translational stroke research · 2021Review
- The P2X7 Receptor in Osteoarthritis.Frontiers in cell and developmental biology · 2021Review
- N-Adamantyl-4-methylthiazol-2-amine suppresses glutamate-induced autophagic cell death via PI3K/Akt/mTOR signaling pathways in cortical neurons.BMB reports · 2020Article
- Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.Cellular and molecular life sciences : CMLS · 2020Article
- mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update.International journal of molecular sciences · 2020Review
- Autophagy-Based Hypothesis on the Role of Brain Catecholamine Response During Stress.Frontiers in psychiatry · 2020Review
- Cell Clearing Systems Bridging Neuro-Immunity and Synaptic Plasticity.International journal of molecular sciences · 2019Review
- Rapamycin in ischemic stroke: Old drug, new tricks?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Review
- Neuroprotection of Cytisine Against Cerebral Ischemia-Reperfusion Injury in Mice by Regulating NR2B-ERK/CREB Signal Pathway.Neurochemical research · 2018Article
- Inhibition of Lysosome Membrane Recycling Causes Accumulation of Gangliosides that Contribute to Neurodegeneration.Cell reports · 2018Article
- The mechanistic target of rapamycin (mTOR) and the silent mating-type information regulation 2 homolog 1 (SIRT1): oversight for neurodegenerative disorders.Biochemical Society transactions · 2018Review
- Interdependency Between Autophagy and Synaptic Vesicle Trafficking: Implications for Dopamine Release.Frontiers in molecular neuroscience · 2018Review
Corrections and comments
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Authors and funding
5 authors.
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Abstract
Excitotoxic insults such as cerebral ischemia are thought to enhance neuronal autophagy, which is then thought to promote neuronal cell death. Excitotoxic insults indeed increase autophagy markers. Notably, however, autophagy markers can be increased either by autophagy induction (as this enhances their production) or by late-stage autophagy inhibition (as this prevents their degradation during autophagic flux). By comparing each condition with and without protease inhibitors that prevent autophagic degradation of the autophagy markers, the results of this study show that excitotoxic glutamate increases autophagy markers by a late-stage block of autophagy. Initially, this study set out to test if the CaMKII inhibitor tatCN21 mediates its post-insult neuroprotection by regulating autophagy. While tatCN21 partially inhibited basal autophagy in hippocampal neurons, it had no effects on the already blocked autophagy after excitotoxic glutamate insults, indicating that autophagy inhibition is not its neuroprotective mechanism. Additionally, while the autophagy inhibitor chloroquine had no effect, significant neuroprotection was seen instead with two drugs that enhance autophagy induction by different mechanisms, rapamycin (mTOR-dependent) and trehalose (mTOR-independent). This suggests that therapeutic approaches should seek to enhance rather than inhibit autophagy, not only in neurodegenerative diseases (where such approach is widely accepted) but also after acute excitotoxic insults. Together, these findings significantly reshape the current view on the mutual cross-regulation of autophagy and excitotoxicity.
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