ArticleBMC neuroscience2018
27-Hydroxycholesterol increases α-synuclein protein levels through proteasomal inhibition in human dopaminergic neurons.
Article in BMC neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 13 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- The Contribution of Type 2 Diabetes to Parkinson's Disease Aetiology.International journal of molecular sciences · 2024Review
- Tissue-Specific Oxysterols as Predictors of Antidepressant (Escitalopram) Treatment Response in Patients With Major Depressive Disorder.Biological psychiatry global open science · 2023Article
- Lipid-lowering drug targets and Parkinson's disease: A sex-specific Mendelian randomization study.Frontiers in neurology · 2022Article
- Autophagy and protein aggregation as a mechanism of dopaminergic degeneration in a primary human dopaminergic neuronal model.Toxicology reports · 2022Article
- The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders.Molecules (Basel, Switzerland) · 2021Review
- The Role of Cholesterol in α-Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Cholesterol Metabolism in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.Molecular neurobiology · 2021Review
- Cholesterol derivatives induce dephosphorylation of the histone deacetylases Rpd3/HDAC1 to upregulate autophagy.Autophagy · 2021Article
- Elevated HDL Levels Linked to Poorer Cognitive Ability in Females With Parkinson's Disease.Frontiers in aging neuroscience · 2021Article
- Cholesterol Metabolism in the Brain and Its Association with Parkinson's Disease.Experimental neurobiology · 2019Review
- The Role of Lipids in Parkinson's Disease.Cells · 2019Review
- Review
Corrections and comments
- Retraction · 2024-11-07Duplication of/in Image · Euphemisms for Duplication · Falsification/Fabrication of Image · Investigation by Company/Institution · Investigation by Journal/Publisher · Investigation by Third Party · Original Data and/or Images not Provided and/or not Available · · See also: https://pubpeer.com/publications/B20869BE4A31AC041BC98E26B3BB11
- Retracted
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAccumulation of the α-synuclein (α-syn) protein is a hallmark of a group of brain disorders collectively known as synucleinopathies. The mechanisms responsible for α-syn accumulation are not well understood. Several studies suggest a link between synucleinopathies and the cholesterol metabolite 27-hydroxycholesterol (27-OHC). 27-OHC is the major cholesterol metabolite in the blood that crosses the blood brain barrier, and its levels can increase following hypercholesterolemia, aging, and oxidative stress, which are all factors for increased synucleinopathy risk. In this study, we determined the extent to which 27-OHC regulates α-syn levels in human dopaminergic neurons, the cell type in which α-syn accumulates in PD, a major synucleinopathy disorder.
resultsOur results show that 27-OHC significantly increases the protein levels, not the mRNA expression of α-syn. The effects of 27-OHC appear to be independent of an action through liver X receptors (LXR), its cognate receptors, as the LXR agonist, GW3965, or the LXR antagonist ECHS did not affect α-syn protein or mRNA levels. Furthermore, our data strongly suggest that the 27-OHC-induced increase in α-syn protein levels emanates from inhibition of the proteasomal degradation of this protein and a decrease in the heat shock protein 70 (HSP70).
conclusionsIdentifying 27-OHC as a factor that can increase α-syn levels and the inhibition of the proteasomal function and reduction in HSP70 levels as potential cellular mechanisms involved in regulation of α-syn. This may help in targeting the correct degradation of α-syn as a potential avenue to preclude α-syn accumulation.
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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.