ArticleScience advances2023
Increased palmitoylation improves estrogen receptor alpha-dependent hippocampal synaptic deficits in a mouse model of synucleinopathy.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 12 citations in OpenAlex.
- ERα Agonist Protects Aged Female Mice From Sevoflurane Neurotoxicity via PTEN Nuclear Translocation.CNS neuroscience & therapeutics · 2026Article
- From lipid modification to cell death: the diverse roles of S-palmitoylation in cell fate decisions.Cell communication and signaling : CCS · 2026Review
- Decorin Attenuates Epileptogenesis and Modulates Hippocampal Synaptic Plasticity via the mTOR Signalling Pathway.Neurochemical research · 2026Article
- Bioinformatics Analysis of ZDHHC-protein Acyltransferase for Predicting the Rupture of Aneurysmal Subarachnoid Hemorrhage.Current neurovascular research · 2026Article
- Sex-dependent immune activation shapes disease progression in a model of Parkinson's disease.Biology of sex differences · 2025Article
- Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline.Annals of neurology · 2025Article
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Review
- Sex Differences in Parkinson's Disease: A Narrative Review.Neurology and therapy · 2025Review
- Protein palmitoylation: an emerging regulator of inflammatory signaling and diseases.Frontiers in immunology · 2025Review
- Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Reducing the lipase LIPE in mutant α-synuclein mice improves Parkinson-like deficits and reveals sex differences in fatty acid metabolism.Neurobiology of disease · 2024Article
- Generation of G51D and 3D mice reveals decreased α-synuclein tetramer-monomer ratios promote Parkinson's disease phenotypes.NPJ Parkinson's disease · 2024Article
- Multi-omics analysis unveils the role of lipid metabolism-derived acylation modifications in POAG and its potential implications.Therapeutic advances in ophthalmologyArticle
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is characterized by conversion of soluble α-synuclein (αS) into intraneuronal aggregates and degeneration of neurons and neuronal processes. Indications that women with early-stage PD display milder neurodegenerative features suggest that female sex partially protects against αS pathology. We previously reported that female sex and estradiol improved αS homeostasis and PD-like phenotypes in E46K-amplified (3K) αS mice. Here, we aimed to further dissect mechanisms that drive this sex dimorphism early in disease. We observed that synaptic abnormalities were delayed in females and improved by estradiol, mediated by local estrogen receptor alpha (ERα). Aberrant ERα distribution in 3K compared to wild-type mice was paired with its decreased palmitoylation. Treatment with ML348, a de-palmitoylation inhibitor, increased ERα availability and soluble αS homeostasis, ameliorating synaptic plasticity and cognitive and motor phenotypes. Our finding that sex differences in early-disease αS-induced synaptic impairment in 3KL mice are in part mediated by palmitoylated ERα may have functional and pathogenic implications for clinical PD.
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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.