ArticleBrain pathology (Zurich, Switzerland)2023
LAMP-2A ablation in hippocampal CA1 astrocytes confers cerebroprotection and ameliorates neuronal injury after global brain ischemia.
Article in Brain pathology (Zurich, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 16 citations in OpenAlex.
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- Dysfunction of hippocampal cells and its role in cognitive impairment.Neural regeneration research · 2026Article
- Bmi1 regulates neural differentiation of mesenchymal stem cells through the Wnt3a‑RhoA signaling pathway to repair ischemic brain injury in rats.International journal of molecular medicine · 2025Article
- Targeting chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapeutic potential.Acta pharmacologica Sinica · 2025Review
- Electrophysiological Signatures in Global Cerebral Ischemia: Neuroprotection Via Chemogenetic Inhibition of CA1 Pyramidal Neurons in Rats.Journal of the American Heart Association · 2024Article
- Chaperone-Mediated Autophagy in Brain Injury: A Double-Edged Sword with Therapeutic Potentials.Molecular neurobiology · 2024Review
- The role of long noncoding ribonucleic acids in the central nervous system injury.Molecular and cellular biochemistry · 2024Review
- N6-methyladenosine demethylase FTO regulates synaptic and cognitive impairment by destabilizing PTEN mRNA in hypoxic-ischemic neonatal rats.Cell death & disease · 2023Article
- Progress in stratified stroke characterization-associated with better diagnosis, accurate prognosis and improved treatment strategies.Brain pathology (Zurich, Switzerland) · 2023Article
- LAMP-2A ablation in hippocampal CA1 astrocytes confers cerebroprotection and ameliorates neuronal injury after global brain ischemia.Brain pathology (Zurich, Switzerland) · 2023Article
- "Adjust Zang and arouse spirit" electroacupuncture ameliorates cognitive impairment by reducing endoplasmic reticulum stress in db/db mice.Frontiers in endocrinology · 2023Article
- The Role of Nrf2 in Relieving Cerebral Ischemia-Reperfusion Injury.Current neuropharmacology · 2023Review
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Reactive astrogliosis and neuronal death are major features of brain tissue damage after transient global cerebral ischemia/reperfusion (I/R). The CA1 subfield in the hippocampus is particularly susceptible to cell death after I/R. Recently, attention has focused on the relationship between the autophagy-lysosomal pathway and cerebral ischemia. Lysosomal-associated membrane protein type-2A (LAMP-2A) is a key protein in chaperone-mediated autophagy (CMA). However, LAMP-2A expression in astrocytes of the hippocampus and its influence on brain injury following I/R remain unknown. Here, we show that LAMP-2A is elevated in astrocytes of the CA1 hippocampal subfield after I/R and in primary cultured astrocytes after transient oxygen-glucose deprivation (OGD). Conditional LAMP-2A knockdown in CA1 astrocytes inhibited astrocyte activation and prevented neuronal death by inhibiting the mitochondrial pathway of apoptosis after I/R, suggesting that elevated astrocytic LAMP-2A contributes to regional ischemic vulnerability. Furthermore, astrocytic LAMP-2A ablation ameliorated the spatial learning and memory deficits caused by I/R. Conditional astrocytic LAMP-2A knockdown also prevented the loss of hippocampal synapses and dendritic spines, improved the synaptic ultrastructure, and inhibited the reduced expression of synaptic proteins after ischemia. Thus, our findings demonstrate that astrocytic LAMP-2A expression increases upon I/R and that LAMP-2A ablation specifically in hippocampal astrocytes contributes to cerebroprotection, suggesting a novel neuroprotective strategy for patients with global ischemia.
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