The cellular and extracellular proteomic signature of human dopaminergic neurons carrying the LRRK2 G2019S mutation DOI Creative Commons
Felix Knab, Giambattista Guaitoli, Mohamed Ali Jarboui

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Dec. 12, 2024

Background Extracellular vesicles are easily accessible in various biofluids and allow the assessment of disease-related changes proteome. This has made them a promising target for biomarker studies, especially field neurodegeneration where access to diseased tissue is very limited. Genetic variants LRRK2 gene have been linked both familial sporadic forms Parkinson’s disease. With inhibitors entering clinical trials, there an unmet need biomarkers that reflect LRRK2-specific pathology engagement. Methods In this study, we used induced pluripotent stem cells derived from patient with disease carrying G2019S mutation isogenic gene-corrected control generate human dopaminergic neurons. We isolated extracellular neuronal cell lysates characterized their proteomic signature using data-independent acquisition proteomics. Then, performed differential expression analysis identify dysregulated proteins mutated line. Metascape ontology enrichment on proteomes associated functional networks. Results identified 595 significantly differentially regulated 3,205 lysates. visualized functionally relevant protein–protein interaction networks key regulators within proteomes. Using ontology, found close association biological processes Finally, focused were cellular provide list ten candidates LRRK2-associated pathology, example, sonic hedgehog signaling molecule, protein tightly LRRK2-related disruption cilia function. Conclusion conclusion, proteome neurons proposed experimentally based future studies.

Language: Английский

Classification and Genotype–Phenotype Relationships of GBA1 Variants: MDSGene Systematic Review DOI Creative Commons
Malco Rossi, Susen Schaake, Tatiana Usnich

et al.

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Depending on zygosity and the specific change, different variants in GBA1 gene can cause Parkinson's disease (PD, PARK-GBA1) with reduced penetrance, act as genetic risk factors for PD or parkinsonism, and/or lead to Gaucher's (GD). This MDSGene systematic literature review covers 27,963 patients carrying from 1082 publications 794 variants, including 13,342 other forms of parkinsonism. It provides a comprehensive overview demographic, clinical, findings an ethnically diverse sample originating 82 countries across five continents. The most frequent pathogenic likely were "N409S" (aka "N370S"; dominating among Jewish Whites), "L483P" "L444P"; Asians Hispanics), whereas common coding "E365K" (E326K), "T408M" (T369M) (both Whites). A novel finding is that early-onset predominantly Asian ethnicity, late-onset mainly White ethnicity. Motor cardinal features similar between motor complications non-motor symptoms more frequently reported "severe" than those "risk" "mild" variants. Cognitive decline was after surgical treatment, despite achieving beneficial function response. Most GD developing harbored variant, Ashkenazi showed positive response chronic levodopa treatment. With this review, we start fill gaps regarding genotype-phenotype correlations variant carriers, especially concerning PD. © 2025 Author(s). Movement Disorders published by Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

Citations

0
The mechanistic view of non-coding RNAs as a regulator of inflammatory pathogenesis of Parkinson’s disease DOI
Yuan Li, Chunlei Yu, Xiaobing Jiang

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 258, P. 155349 - 155349

Published: May 16, 2024

Language: Английский

Citations

2
The cellular and extracellular proteomic signature of human dopaminergic neurons carrying the LRRK2 G2019S mutation DOI Creative Commons
Felix Knab, Giambattista Guaitoli, Mohamed Ali Jarboui

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Dec. 12, 2024

Background Extracellular vesicles are easily accessible in various biofluids and allow the assessment of disease-related changes proteome. This has made them a promising target for biomarker studies, especially field neurodegeneration where access to diseased tissue is very limited. Genetic variants LRRK2 gene have been linked both familial sporadic forms Parkinson’s disease. With inhibitors entering clinical trials, there an unmet need biomarkers that reflect LRRK2-specific pathology engagement. Methods In this study, we used induced pluripotent stem cells derived from patient with disease carrying G2019S mutation isogenic gene-corrected control generate human dopaminergic neurons. We isolated extracellular neuronal cell lysates characterized their proteomic signature using data-independent acquisition proteomics. Then, performed differential expression analysis identify dysregulated proteins mutated line. Metascape ontology enrichment on proteomes associated functional networks. Results identified 595 significantly differentially regulated 3,205 lysates. visualized functionally relevant protein–protein interaction networks key regulators within proteomes. Using ontology, found close association biological processes Finally, focused were cellular provide list ten candidates LRRK2-associated pathology, example, sonic hedgehog signaling molecule, protein tightly LRRK2-related disruption cilia function. Conclusion conclusion, proteome neurons proposed experimentally based future studies.

Language: Английский

Citations

0