ArticleCells2021
Unexpected Implication of SRP and AGO2 in Parkinson's Disease: Involvement in Alpha-Synuclein Biogenesis.
Article in Cells, 2021. 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, 15 citations in OpenAlex.
- Human SRP Subunits Coordinate Protein Targeting and mRNA Quality Control.bioRxiv : the preprint server for biology · 2026Article
- Structural insights into disease-associated mutations in the microRNA processing machinery.Experimental & molecular medicine · 2026Review
- Proximity labeling reveals non-catalytic interactions between DPP9 and ubiquitin signaling complexes.Cellular and molecular life sciences : CMLS · 2026Article
- Circular RNA: From non-coding regulators to functional protein encoders.Pharmaceutical science advances · 2025Review
- A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration.Nature communications · 2025Article
- Network Analysis Performed on Transcriptomes of Parkinson's Disease Patients Reveals Dysfunction in Protein Translation.International journal of molecular sciences · 2024Article
- The Common Denominators of Parkinson's Disease Pathogenesis and Methamphetamine Abuse.Current neuropharmacology · 2024Review
- Amyloid Precursor Protein and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The use of RNA-based treatments in the field of cancer immunotherapy.Molecular cancer · 2023Review
- Article
- Aberrant protein targeting activates quality control on the ribosome.Frontiers in cell and developmental biology · 2023Article
- Defective Human SRP Induces Protein Quality Control and Triggers Stress Response.Journal of molecular biology · 2022Article
- Signal Recognition Particle in Human Diseases.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder classified by the loss of dopaminergic neurons in the substantia nigra pars compacta, the region of the brain that is responsible for motor control. Surviving neurons in this region contain aggregated protein alpha-Synuclein (αSyn) in the form of cytoplasmic inclusions, referred to as Lewy bodies. Changes in αSyn expression are also associated with PD and its progression. Previously, we demonstrated that signal recognition particle (SRP) and Argonaute 2 (AGO2) proteins are involved in protein quality control at the ribosome during translation. We also demonstrated that SRP has an mRNA protection function in addition to a protein targeting function, thus controlling mRNA and protein expression. In this study, we tested involvement of these factors in αSyn biogenesis. We hypothesize that loss of these factors may interfere with αSyn expression, and subsequently, be associated with PD. Using depletion assays in human cell culture and analysis of these proteins in the brains of deceased PD patients, we demonstrate that SRP and AGO2 are involved in the control of αSyn expression and AGO2 has reduced expression in PD. We show for the first time that SRP is involved in mRNA protection of αSyn, a protein that does not have a signal sequence or transmembrane span. Our findings suggest that SRP may interact with a hydrophobic domain in the middle of αSyn during translation. Understanding the molecular mechanisms controlling αSyn biogenesis in cells is vital to developing preventative therapies against PD.
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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.