دورية
Distinct sets of lysosomal genes define synucleinopathy and tauopathy.
| العنوان: | Distinct sets of lysosomal genes define synucleinopathy and tauopathy. |
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| المؤلفون: | Oh KW; Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea., Kim DK; Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea., Hsu AL; Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 112-304, Taiwan., Lee SJ; Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; Convergence Research Center for Dementia, Seoul National University College of Medicine, Seoul 03081; Neuramedy Co. Ltd., Seoul 04796, Korea. |
| المصدر: | BMB reports [BMB Rep] 2023 Dec; Vol. 56 (12), pp. 657-662. |
| نوع المنشور: | News |
| اللغة: | English |
| بيانات الدورية: | Publisher: Korean Society for Biochemistry and Molecular Biology Country of Publication: Korea (South) NLM ID: 101465334 Publication Model: Print Cited Medium: Internet ISSN: 1976-670X (Electronic) Linking ISSN: 19766696 NLM ISO Abbreviation: BMB Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Seoul : Korean Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Synucleinopathies* , Tauopathies*/genetics , Proteostasis Deficiencies*, Animals ; Humans ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Protein Aggregates ; tau Proteins/genetics ; tau Proteins/metabolism ; Lysosomes/genetics ; Lysosomes/metabolism |
| مستخلص: | Neurodegenerative diseases are characterized by distinct protein aggregates, such as those of α-synuclein and tau. Lysosomal defect is a key contributor to the accumulation and propagation of aberrant protein aggregates in these diseases. The discoveries of common proteinopathies in multiple forms of lysosomal storage diseases (LSDs) and the identification of some LSD genes as susceptible genes for those proteinopathies suggest causative links between LSDs and the proteinopathies. The present study hypothesized that defects in lysosomal genes will differentially affect the propagation of α-synuclein and tau proteins, thereby determining the progression of a specific proteinopathy. We established an imaging-based high-contents screening (HCS) system in Caenorhabditis elegans (C. elegans) model, by which the propagation of α-synuclein or tau is measured by fluorescence intensity. Using this system, we performed RNA interference (RNAi) screening to induce a wide range of lysosomal malfunction through knock down of 79 LSD genes, and to obtain the candidate genes with significant change in protein propagation. While some LSD genes commonly affected both α-synuclein and tau propagation, our study identified the distinct sets of LSD genes that differentially regulate the propagation of either α-synuclein or tau. The specificity and efficacy of these LSD genes were retained in the disease-related phenotypes, such as pharyngeal pumping behavior and life span. This study suggests that distinct lysosomal genes differentially regulate the propagation of α-synuclein and tau, and offer a steppingstone to understanding disease specificity. [BMB Reports 2023; 56(12): 657-662]. |
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| المشرفين على المادة: | 0 (alpha-Synuclein) 0 (Protein Aggregates) 0 (tau Proteins) |
| تواريخ الأحداث: | Date Created: 20231011 Date Completed: 20231229 Latest Revision: 20240308 |
| رمز التحديث: | 20240308 |
| مُعرف محوري في PubMed: | PMC10761752 |
| PMID: | 37817435 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1976-670X |
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