ArticleeNeuro
SCD Inhibition Protects from α-Synuclein-Induced Neurotoxicity But Is Toxic to Early Neuron Cultures.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 17 citations in OpenAlex.
- Quantifying the Acute Toxicity of Alpha-Synuclein Membrane-Accumulation in a Cell-Based Assay.Journal of molecular neuroscience : MN · 2026Article
- Elevation of Stearoyl-Coenzyme A Desaturase and Monounsaturated Fatty Acids in Parkinson's Disease Serum.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Stearoyl-CoA desaturase 5 (SCD5) in lipid remodeling: From molecular control to pathophysiology.Journal of lipid research · 2026Review
- Astrocytic ACSBG1 depletion improves lipid-cytokine signaling and attenuates α-Synuclein pathology in a Parkinson's disease mouse model.bioRxiv : the preprint server for biology · 2026Article
- Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025Review
- Dysregulation of Monounsaturated Fatty Acids is Related to α-Synuclein in Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- A guide to selecting high-performing antibodies for Stearoyl-CoA desaturase (SCD1) (UniProt ID: O00767) for use in western blot, immunoprecipitation, and immunofluorescence.F1000Research · 2025Article
- Stearoyl-CoA desaturase-1: a potential therapeutic target for neurological disorders.Molecular neurodegeneration · 2024Review
- Interactions of alpha-synuclein with membranes in Parkinson's disease: Mechanisms and therapeutic strategies.Neurobiology of disease · 2024Review
- Central inhibition of stearoyl-CoA desaturase has minimal effects on the peripheral metabolic symptoms of the 3xTg Alzheimer's disease mouse model.Scientific reports · 2024Article
- Non-clinical Pharmacology of YTX-7739: a Clinical Stage Stearoyl-CoA Desaturase Inhibitor Being Developed for Parkinson's Disease.Molecular neurobiology · 2022Article
- Pathogenic Mechanisms of Cytosolic and Membrane-Enriched α-Synuclein Converge on Fatty Acid Homeostasis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Lipotoxicity Downstream of α-Synuclein Imbalance: A Relevant Pathomechanism in Synucleinopathies?Biomolecules · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here, we report the independent discovery and validation of stearoyl-CoA desaturase (SCD) as a modulator of α-synuclein (αSyn)-induced pathology and toxicity in cell-based Parkinson's disease (PD) models. We identified SCD as top altered gene from transcriptional profiling in primary neurons exogenously expressing αSyn with the amplified familial PD mutation 3K. Thus, we sought to further explore SCD as a therapeutic target in neurodegeneration. We report that SCD inhibitors are toxic to early human and rat neuron cultures while displaying minimal toxicity to late cultures. The fatty acid product of SCD, oleic acid (OLA), fully rescues this toxicity in early cultures, suggesting on-target toxicity. Furthermore, SCD inhibition rescues αSyn 3K-induced toxicity in late primary neurons. We also confirm that SCD inhibitors reduce formation of αSyn accumulations, while OLA increases these accumulations in an αSyn 3K neuroblastoma model. However, we identify a caveat with this model where αSyn 3K levels can be suppressed by high SCD inhibitor concentrations, obscuring true effect size. Further, we show that both SCD1 or SCD5 knock-down reduce αSyn 3K accumulations and toxicity, making both a putative drug target. Overall, we confirm key findings of published data on SCD inhibition and its benefits in αSyn accumulation and stress models. The differential neurotoxicity induced by SCD inhibition based on neuron culture age must be accounted for when researching SCD in neuron models and has potential clinical implications. Lastly, our gene profiling studies also revealed novel putative genes connected to αSyn neurotoxicity that are worth further study.
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.