ArticleAutophagy2021
Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal storage and associated synaptic impairments in neurons.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 212 citations in OpenAlex.
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
- Cystatin C and its Role in the Neuro-Glial-Vascular Unit: Implications for Cerebrovascular Diseases and Neurodegeneration.Neuroscience bulletin · 2026Review
- β-Adducin Restrains PLA2G4A-Dependent Lysosomal Membrane Permeabilization and Neuronal Death in Ischemic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MCOLN1-mediated PPP3CB activation alleviates neuronal damage by promoting TFEB-dependent autophagic flux in permanent cerebral ischemia.Acta pharmacologica Sinica · 2026Article
- PIP4K2A Attenuates Cerebral Ischemia/Reperfusion Injury by Reducing the TRIB3-p62 Complex Burden and Modulating AKT/mTOR Signaling.Translational stroke research · 2026Article
- Systematic Identification of Therapeutic Targets and Repurposed Drugs for Stroke: From Genome Causal Analysis to Multilevel Validation.Journal of the American Heart Association · 2026Article
- The intrinsic excitability of and autophagy protein expression levels in dentate gyrus ensembles regulate fear generalization.Neural regeneration research · 2026Article
- Targeting microglial circMBNL1 unlocks a novel nanomedicine therapeutic strategy for major depressive disorder.Journal of nanobiotechnology · 2026Article
- Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Lipophagy in disease: signaling control, organelle communication, and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- NIBV Induces Incomplete Autophagy via AMPK-TFEB, Causing Kidney Injury in Chicks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Uncovering the Key Circuit FOSL2/FOS/EGR3/EGR1, Contributing to the Hyperexcitability of Excitatory Neurons in the Epileptic Temporal Cortex and Hippocampus.International journal of molecular sciences · 2026Article
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- Peiminine-Induced Selective Autophagy of AIM2 Inflammasomes Rescues Cerebral Ischemic Injury.Journal of the American Heart Association · 2026Article
- HIF-1α/BNIP3-mediated mitophagy mitigates cerebral ischemia/reperfusion injury in rats by suppressing NLRP3 inflammasome activation.European journal of medical research · 2026Article
- Astrocytic mitochondrial transfer: a new horizon for metabolic rescue and precision therapy in ischemic stroke.Journal of translational medicine · 2026Review
- The mTOR/Akt pathway is involved in regulating astrocyte growth and GLT-1 expression during cerebral ischemia-reperfusion.PloS one · 2026Article
- Adipose-derived stem cell-conditioned medium mitigates ischemia-induced neuronal injury via the JAK1/STAT3 signaling pathway.Frontiers in cellular neuroscience · 2026Article
- Selective autophagy inhibition alleviates oxidative stress-associated neurodegeneration in an AD+CCH model.Frontiers in aging neuroscience · 2026Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macroautophagy/autophagy is vital for neuronal homeostasis and functions. Accumulating evidence suggest that autophagy is impaired during cerebral ischemia, contributing to neuronal dysfunction and neurodegeneration. However, the outcomes after transient modification in autophagy machinery are not fully understood. This study investigated the effects of ischemic stress on autophagy and synaptic structures using a rat model of oxygen-glucose deprivation (OGD) in hippocampal neurons and a mouse model of middle cerebral artery occlusion (MCAO). Upon acute ischemia, an initial autophagy modification occurred in an upregulation manner. Following, the number of lysosomes increased, as well as lysosomal volume, indicating dysfunctional lysosomal storage. These changes were prevented by inhibiting autophagy via 3-methyladenine (3-MA) treatment or ATG7 (autophagy related 7) knockdown, or were mimicked by rapamycin (RAPA), a known activator of autophagy. This suggests that dysfunctional lysosomal storage is associated with the early burst of autophagy. Dysfunctional lysosomal storage contributed to autophagy dysfunction because the basal level of MTOR-dependent lysosomal biogenesis in the reperfusion was not sufficient to clear undegraded cargoes after transient autophagy upregulation. Further investigation revealed that impairment of synaptic ultra-structures, accompanied by dysfunctional lysosomal storage, may result from a failure in dynamic turnover of synaptic proteins. This indicates a vital role of autophagy-lysosomal machinery in the maintenance of synaptic structures. This study supports previous evidence that dysfunctional lysosomal storage may occur following the upregulation of autophagy in neurons. Appropriate autophagosome-lysosomal functioning is vital for maintenance of neuronal synaptic function and impacts more than the few known synaptic proteins.
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Registered trials
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.