ArticleCellular signalling2014
Activation of AMPK and inactivation of Akt result in suppression of mTOR-mediated S6K1 and 4E-BP1 pathways leading to neuronal cell death in in vitro models of Parkinson's disease.
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 165 citations in OpenAlex.
- SGLT2 Inhibitors Promote Diabetic Wound Healing Via AMPK/AKT/mTORC1-Regulated Endothelial Angiogenesis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Narrative Review "Dual Frontiers in Neurodegeneration: Pharmacological Synergies and Divergences in Parkinson's Disease and Type 2 Diabetes Mellitus".Cellular and molecular neurobiology · 2026Review
- Unveiling the therapeutic potential of Farnesol against Parkinson's disease: insights from molecular Docking and animal studies.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Rapamycin and Autophagy: Potential Therapeutic Approach for Parkinson's Disease Treatment.CNS & neurological disorders drug targets · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Downregulation of AKT-mediated p27IBRO neuroscience reports · 2025Article
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Neurotoxic Effects of Atrazine on Dopaminergic System via miRNAs and Energy-Sensing Pathways.Molecular neurobiology · 2025Article
- Intracerebellar upregulation of Rheb(S16H) ameliorates motor dysfunction in mice with SCA2.Acta pharmacologica Sinica · 2025Article
- Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism.Aging and disease · 2025Review
- Glutamate increases the lean percentage and intramuscular fat content and alters gut microbiota in Shaziling pigs.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- Exploring the link between estimated glucose disposal rate and Parkinson's disease: cross-sectional and mortality analysis of NHANES 2003-2016.Frontiers in aging neuroscience · 2025Article
- Parkinson's disease and metabolic disorders, understanding their shared co-morbidity through the autonomic nervous system.Advances in genetics · 2025Review
- Alcohol induces p53-mediated apoptosis in neural crest by stimulating an AMPK-mediated suppression of TORC1, S6K, and ribosomal biogenesis.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms.Journal of neuroinflammation · 2024Review
- Trehalose Attenuates In Vitro Neurotoxicity of 6-Hydroxydopamine by Reducing Oxidative Stress and Activation of MAPK/AMPK Signaling Pathways.International journal of molecular sciences · 2024Article
- Unraveling the AKT/ERK cascade and its role in Parkinson disease.Archives of toxicology · 2024Review
- LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.CNS & neurological disorders drug targets · 2024Review
- Mitochondrial Hydrogen Peroxide Activates PTEN and Inactivates Akt Leading to Autophagy Inhibition-Dependent Cell Death in Neuronal Models of Parkinson's Disease.Molecular neurobiology · 2023Article
27 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
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. Dysregulation of mammalian target of rapamycin (mTOR) has been implicated in the pathogenesis of PD. However, the underlying mechanism is incompletely elucidated. Here, we show that PD mimetics (6-hydroxydopamine, N-methyl-4-phenylpyridine or rotenone) suppressed phosphorylation of mTOR, S6K1 and 4E-BP1, reduced cell viability, and activated caspase-3 and PARP in PC12 cells and primary neurons. Overexpression of wild-type mTOR or constitutively active S6K1, or downregulation of 4E-BP1 in PC12 cells partially prevented cell death in response to the PD toxins, revealing that mTOR-mediated S6K1 and 4E-BP1 pathways due to the PD toxins were inhibited, leading to neuronal cell death. Furthermore, we found that the inhibition of mTOR signaling contributing to neuronal cell death was attributed to suppression of Akt and activation of AMPK. This is supported by the findings that ectopic expression of constitutively active Akt or dominant negative AMPKα, or inhibition of AMPKα with compound C partially attenuated inhibition of phosphorylation of mTOR, S6K1 and 4E-BP1, activation of caspase-3, and neuronal cell death triggered by the PD toxins. The results indicate that PD stresses activate AMPK and inactivate Akt, causing neuronal cell death via inhibiting mTOR-mediated S6K1 and 4E-BP1 pathways. Our findings suggest that proper co-manipulation of AMPK/Akt/mTOR signaling may be a potential strategy for prevention and treatment of PD.
Indexed as
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.