ArticleCell death discovery2021
BH3-only proteins Puma and Beclin1 regulate autophagic death in neurons in response to Amyloid-β.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- The Central Role of Neuronal Cell Death in Alzheimer's Disease Pathobiology.Biomedicines · 2026Review
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- CDC25C downregulation suppresses HCC growth via mitochondrial stress-induced autophagy and apoptosis.Scientific reports · 2026Article
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Review
- TIMP-1 enhances Akt and BDNF signaling in neurons to reduce synaptic and cognitive deficits in 5xFAD mouse model of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- [Mechanism of BIM-induced ibrutinib resistance in chronic lymphocytic leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Therapeutic effects ofFrontiers in pharmacology · 2025Article
- Caspases in Alzheimer's Disease: Mechanism of Activation, Role, and Potential Treatment.Molecular neurobiology · 2024Review
- FoxG1 as a Potential Therapeutic Target for Alzheimer's Disease: Modulating NLRP3 Inflammasome via AMPK/mTOR Autophagy Pathway.Cellular and molecular neurobiology · 2024Article
- Defective quality control autophagy in Hyperhomocysteinemia promotes ER stress and consequent neuronal apoptosis through proteotoxicity.Cell communication and signaling : CCS · 2023Article
- Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways.Pharmaceutics · 2023Article
- The Molecular Mechanisms of Neuroinflammation in Alzheimer's Disease, the Consequence of Neural Cell Death.International journal of molecular sciences · 2023Review
- The inhibition of ORMDL3 prevents Alzheimer's disease through ferroptosis by PERK/ATF4/HSPA5 pathway.IET nanobiotechnology · 2023Article
- Peroxiredoxin 2 Ameliorates AβO-Mediated Autophagy by Inhibiting ROS via the ROS-NRF2-p62 Pathway in N2a-APP Swedish Cells.Antioxidants (Basel, Switzerland) · 2022Article
- The role of BCL-2 family proteins in regulating apoptosis and cancer therapy.Frontiers in oncology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is characterized by accumulation of senile amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles causing progressive loss of synapse and neuronal death. Out of the various neuron death modalities, autophagy and apoptosis are reported to be the major death paradigms in AD. However, how these two processes lead to neuronal loss is still inconspicuous. Here we report that under Aβ toxicity, aberrant autophagy is induced with inefficient autophagic flux in neurons. Simultaneous activation of both autophagy and apoptosis are seen in primary cortical neurons as well as in transgenic mice brains. We found that induction of autophagy by rapamycin is detrimental for neurons; whereas downregulation of Beclin1, an important autophagy inducing protein, provides significant protection in Aβ treated neuronal cells by blocking cytochrome-c release from the mitochondria. We further report that downregulation of Puma, a BH3-only pro-apoptotic protein, inhibits the induction of aberrant autophagy and also ameliorates the autophagy flux under the influence of Aβ. Notably, stereotactic administration of shRNAs against Puma and Beclin1 in adult Aβ-infused rat brains inhibits both apoptotic and autophagic pathways. The regulation of both of the death processes is brought about by the direct interaction between Puma and Beclin1 upon Aβ treatment. We conclude that both Beclin1 and Puma play essential roles in the neuronal death caused by the induction of aberrant autophagy in AD and targeting their interaction could be vital to understand the crosstalk of autophagy and apoptosis as well as to develop a potential therapeutic strategy in AD.
Identifiers
What OpenQuestion holds
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.