ArticleNPJ Parkinson's disease2023
Regulators of proteostasis are translationally repressed in fibroblasts from patients with sporadic and LRRK2-G2019S Parkinson's disease.
Article in NPJ Parkinson's disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A.Molecular neurodegeneration advances · 2026Article
- Article
- RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system.Journal of advanced research · 2025Review
- Comparing loss of individual fragile X proteins suggests strong links to cellular senescence and aging.Cellular and molecular life sciences : CMLS · 2025Article
- In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson's disease.Brain : a journal of neurology · 2025Article
- A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration.Nature communications · 2025Article
- Review
- Single-nucleus multi-omics of Parkinson's disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks.Acta neuropathologica communications · 2024Article
- Protein Translation in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2024Review
- Impaired Mitochondrial Network Morphology and Reactive Oxygen Species Production in Fibroblasts from Parkinson's Disease Patients.Biomedicines · 2024Article
- Early-stage idiopathic Parkinson's disease is associated with reduced circular RNA expression.NPJ Parkinson's disease · 2024Article
- Progressive Motor and Non-Motor Symptoms inInternational journal of molecular sciences · 2023Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deficits in protein synthesis are associated with Parkinson's disease (PD). However, it is not known which proteins are affected or if there are synthesis differences between patients with sporadic and Leucine-Rich Repeat Kinase 2 (LRRK2) G2019S PD, the most common monogenic form. Here we used bio-orthogonal non-canonical amino acid tagging for global analysis of newly translated proteins in fibroblasts from sporadic and LRKK2-G2019S patients. Quantitative proteomic analysis revealed that several nascent proteins were reduced in PD samples compared to healthy without any significant change in mRNA levels. Using targeted proteomics, we validated which of these proteins remained dysregulated at the static proteome level and found that regulators of endo-lysosomal sorting, mRNA processing and components of the translation machinery remained low. These proteins included autophagy-related protein 9A (ATG9A) and translational stability regulator YTH N6-ethyladenosine RNA binding protein 3 (YTHDF3). Notably, 77% of the affected proteins in sporadic patients were also repressed in LRRK2-G2019S patients (False discovery rate (FDR) < 0.05) in both sporadic and LRRK2-G2019S samples. This analysis of nascent proteomes from PD patient skin cells reveals that regulators of proteostasis are repressed in both sporadic and LRRK2-G2019S PD.
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Registered trials
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