ArticleThe Journal of biological chemistry2021
The AKT modulator A-443654 reduces α-synuclein expression and normalizes ER stress and autophagy.
Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 36 citations in OpenAlex.
- Neuroprotection Across Cerebellar and Nigrostriatal Degeneration: Translational Insights from Parkinson's Disease to Spinocerebellar Ataxia Type 2.Cerebellum (London, England) · 2026Review
- Article
- SIMD: Synergistic integration mutualistic platform based on single-cell and proteotranscriptomics for drug repositioning.NPJ breast cancer · 2025Article
- Targeting STAU1 prevents p53 apoptotic signaling in neurodegeneration.Cell death & disease · 2025Article
- Stem Cell-Based Approaches in Parkinson's Disease Research.International journal of stem cells · 2025Review
- Article
- The effect of AKT inhibition in α-synuclein-dependent neurodegeneration.Frontiers in molecular neuroscience · 2025Article
- Mitochondrial oxidant stress promotes α-synuclein aggregation and spreading in mice with mutated glucocerebrosidase.NPJ Parkinson's disease · 2024Article
- In vitro modulation of mTOR and mGlur5 influence α-synuclein accumulation.Molecular brain · 2024Article
- Can pluripotent/multipotent stem cells reverse Parkinson's disease progression?Frontiers in neuroscience · 2024Review
- TRPV4-mediated CaFASEB bioAdvances · 2023Article
- Strategies targeting endoplasmic reticulum stress to improve Parkinson's disease.Frontiers in pharmacology · 2023Review
- System analysis based on the pyroptosis-related genes identifies GSDMC as a novel therapy target for pancreatic adenocarcinoma.Journal of translational medicine · 2022Article
- Induced pluripotent stem cells: a tool for modeling Parkinson's disease.Trends in neurosciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Accumulation of α-synuclein is a main underlying pathological feature of Parkinson's disease and α-synucleinopathies, for which lowering expression of the α-synuclein gene (SNCA) is a potential therapeutic avenue. Using a cell-based luciferase reporter of SNCA expression we performed a quantitative high-throughput screen of 155,885 compounds and identified A-443654, an inhibitor of the multiple functional kinase AKT, as a potent inhibitor of SNCA. HEK-293 cells with CAG repeat expanded ATXN2 (ATXN2-Q58 cells) have increased levels of α-synuclein. We found that A-443654 normalized levels of both SNCA mRNA and α-synuclein monomers and oligomers in ATXN2-Q58 cells. A-443654 also normalized levels of α-synuclein in fibroblasts and iPSC-derived dopaminergic neurons from a patient carrying a triplication of the SNCA gene. Analysis of autophagy and endoplasmic reticulum stress markers showed that A-443654 successfully prevented α-synuclein toxicity and restored cell function in ATXN2-Q58 cells, normalizing the levels of mTOR, LC3-II, p62, STAU1, BiP, and CHOP. A-443654 also decreased the expression of DCLK1, an inhibitor of α-synuclein lysosomal degradation. Our study identifies A-443654 and AKT inhibition as a potential strategy for reducing SNCA expression and treating Parkinson's disease pathology.
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.