ArticleScience signaling2020
Activation of the Akt1-CREB pathway promotes
Article in Science signaling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Oleuropein regulates neuronal survival and Histone acetylation in Parkinson's disease: cellular and epigenetic insights.Metabolic brain disease · 2026Article
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- Gut microbial production of imidazole propionate drives Parkinson's pathologies.Nature communications · 2025Article
- Using network toxicology and molecular docking to identify core targets and pathways underlying tacrolimus-induced tremor in organ transplant recipients.Scientific reports · 2025Article
- Exploring the active ingredients and potential mechanisms of Pingchan granules in Parkinson's disease treatment through network pharmacology and transcriptomics.Scientific reports · 2025Article
- Targeting the PARylation-Dependent Ubiquitination Signaling Pathway for Cancer Therapies.Biomolecules · 2025Review
- Black ginseng under forest as a natural antidepressant: insights into its active components and mechanisms.Frontiers in chemistry · 2025Article
- Mirodenafil improves cognitive function by reducing microglial activation and blood-brain barrier permeability in ApoE4 KI mice.Frontiers in aging neuroscience · 2025Article
- The Role of Dectin-1-Akt-RNF146 Pathway in β-Glucan Induced Immune Trained State of Monocyte in Sepsis.Journal of inflammation research · 2025Article
- Contrastive machine learning reveals Parkinson's disease specific features associated with disease severity and progression.Communications biology · 2024Article
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- SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model.Cell reports. Medicine · 2024Article
- Molecular targets and mechanisms of Sijunzi decoction in the treatment of Parkinson's disease: evidence from network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation.Frontiers in pharmacology · 2024Article
- Neurotoxic properties of the Zika virus envelope protein.Experimental neurology · 2023Article
- Chlorogenic Acid and Caffeine in Coffee Restore Insulin Signaling in Pancreatic Beta Cells.The Kobe journal of medical sciences · 2023Article
- DRR1 promotes neuroblastoma cell differentiation by regulating CREB expression.Pediatric research · 2023Article
- Effects of the compound extracts ofFrontiers in microbiology · 2023Article
- Mechanism of Tianma Gouteng Decoction in the treatment of Parkinson's disease based on network pharmacology and molecular docking.American journal of translational research · 2023Article
- Mechanism of Gynostemmae Pentaphylli Herba in the treatment of ischemic stroke based on network pharmacology and molecular docking.American journal of translational research · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Progressive degeneration of dopaminergic neurons characterizes Parkinson's disease (PD). This neuronal loss occurs through diverse mechanisms, including a form of programmed cell death dependent on poly(ADP-ribose) polymerase-1 (PARP1) called parthanatos. Deficient activity of the kinase Akt1 and aggregation of the protein α-synuclein are also implicated in disease pathogenesis. Here, we found that Akt1 suppressed parthanatos in dopaminergic neurons through a transcriptional mechanism. Overexpressing constitutively active Akt1 in SH-SY5Y cells or culturing cells with chlorogenic acid (a polyphenol found in coffee that activates Akt1) stimulated the CREB-dependent transcriptional activation of the gene encoding the E3 ubiquitin ligase RNF146. RNF146 inhibited PARP1 not through its E3 ligase function but rather by binding to and sequestering PAR, which enhanced the survival of cultured cells exposed to the dopaminergic neuronal toxin 6-OHDA or α-synuclein aggregation. In mice, intraperitoneal administration of chlorogenic acid activated the Akt1-CREB-RNF146 pathway in the brain and provided neuroprotection against both 6-OHDA and combinatorial α-synucleinopathy in an RNF146-dependent manner. Furthermore, dysregulation of the Akt1-CREB pathway was observed in postmortem brain samples from patients with PD. The findings suggest that therapeutic restoration of
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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.