ArticlePloS one2013
Inhibition of PIKfyve by YM-201636 dysregulates autophagy and leads to apoptosis-independent neuronal cell death.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 91 citations in OpenAlex.
- PIKfyve mediates the maturation of mycobacteria-containing vesicles.Frontiers in cellular and infection microbiology · 2026Article
- In silico discovery and experimental validation of natural derivatives as inhibitor of phosphoinositide Kinase, PIKfyve.Journal of computer-aided molecular design · 2025Article
- Poly-GP accumulation due to C9orf72 loss of function induces motor neuron apoptosis through autophagy and mitophagy defects.Autophagy · 2024Article
- A PIKfyve modulator combined with an integrated stress response inhibitor to treat lysosomal storage diseases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.Medicinal research reviews · 2023Review
- Discovery of a First-in-Class Degrader for the Lipid Kinase PIKfyve.Journal of medicinal chemistry · 2023Article
- Advances in Drug Discovery Targeting Lysosomal Membrane Proteins.Pharmaceuticals (Basel, Switzerland) · 2023Review
- A plant virus hijacks phosphatidylinositol-3,5-bisphosphate to escape autophagic degradation in its insect vector.Autophagy · 2023Article
- The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system.Journal of cell science · 2023Article
- Development of a Covalent Inhibitor of c-Jun N-Terminal Protein Kinase (JNK) 2/3 with Selectivity over JNK1.Journal of medicinal chemistry · 2023Article
- Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses.Journal of medicinal chemistry · 2022Article
- Endosome maturation links PI3Kα signaling to lysosome repopulation during basal autophagy.The EMBO journal · 2022Article
- Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia.Cancers · 2022Review
- Effect of empagliflozin on cytoskeletal repair in the hippocampus of obese mice.Frontiers in neuroscience · 2022Article
- Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection.Inflammopharmacology · 2021Review
- Dissecting lipid metabolism alterations in SARS-CoV-2.Progress in lipid research · 2021Review
- The M1311V variant of ATP7A is associated with impaired trafficking and copper homeostasis in models of motor neuron disease.Neurobiology of disease · 2021Article
- The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2), synthesised by PIKfyve, regulates a number of intracellular membrane trafficking pathways. Genetic alteration of the PIKfyve complex, leading to even a mild reduction in PtdIns(3,5)P 2, results in marked neurodegeneration via an uncharacterised mechanism. In the present study we have shown that selectively inhibiting PIKfyve activity, using YM-201636, significantly reduces the survival of primary mouse hippocampal neurons in culture. YM-201636 treatment promoted vacuolation of endolysosomal membranes followed by apoptosis-independent cell death. Many vacuoles contained intravacuolar membranes and inclusions reminiscent of autolysosomes. Accordingly, YM-201636 treatment increased the level of the autophagosomal marker protein LC3-II, an effect that was potentiated by inhibition of lysosomal proteases, suggesting that alterations in autophagy could be a contributing factor to neuronal cell death.
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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.