Pub Date : 2024-08-28DOI: 10.1101/2023.04.09.536178
Shiyi Wang, Ryan Baumert, Gabrielle Séjourné, Dhanesh Sivadasan Bindu, Kylie Dimond, Kristina Sakers, Leslie Vazquez, Jessica Moore, Christabel Xin Tan, Tetsuya Takano, Maria Pia Rodriguez, Scott H Soderling, Albert R La Spada, Cagla Eroglu
Astrocytes, a major glial cell type of the brain, regulate synapse numbers and function. However, whether astrocyte dysfunction can cause synaptic pathologies in neurological disorders such as Parkinson's Disease (PD) is unknown. Here, we investigated the impact of the most common PD-linked mutation in the leucine-rich repeat kinase 2 (LRRK2) gene (G2019S) on the synaptic functions of astrocytes. We found that both in human and mouse cortex, the LRRK2 G2019S mutation causes astrocyte morphology deficits and enhances the phosphorylation of the ERM proteins (Ezrin, Radixin, and Moesin), which are important components of perisynaptic astrocyte processes. Reducing ERM phosphorylation in LRRK2 G2019S mouse astrocytes restored astrocyte morphology and corrected excitatory synaptic deficits. Using an in vivo BioID proteomic approach, we found Ezrin, the most abundant astrocytic ERM protein, interacts with the Autophagy-Related 7 (Atg7), a master regulator of catabolic processes. The Ezrin/Atg7 interaction is inhibited by Ezrin phosphorylation, thus diminished in the LRRK2 G2019S astrocytes. Importantly, Atg7 function is required to maintain proper astrocyte morphology. These studies reveal an astrocytic molecular mechanism that could serve as a therapeutic target in PD.
{"title":"Astrocytic LRRK2 Controls Synaptic Connectivity via Regulation of ERM Phosphorylation.","authors":"Shiyi Wang, Ryan Baumert, Gabrielle Séjourné, Dhanesh Sivadasan Bindu, Kylie Dimond, Kristina Sakers, Leslie Vazquez, Jessica Moore, Christabel Xin Tan, Tetsuya Takano, Maria Pia Rodriguez, Scott H Soderling, Albert R La Spada, Cagla Eroglu","doi":"10.1101/2023.04.09.536178","DOIUrl":"10.1101/2023.04.09.536178","url":null,"abstract":"<p><p>Astrocytes, a major glial cell type of the brain, regulate synapse numbers and function. However, whether astrocyte dysfunction can cause synaptic pathologies in neurological disorders such as Parkinson's Disease (PD) is unknown. Here, we investigated the impact of the most common PD-linked mutation in the leucine-rich repeat kinase 2 (<i>LRRK2</i>) gene (G2019S) on the synaptic functions of astrocytes. We found that both in human and mouse cortex, the LRRK2 G2019S mutation causes astrocyte morphology deficits and enhances the phosphorylation of the ERM proteins (Ezrin, Radixin, and Moesin), which are important components of perisynaptic astrocyte processes. Reducing ERM phosphorylation in LRRK2 G2019S mouse astrocytes restored astrocyte morphology and corrected excitatory synaptic deficits. Using an <i>in vivo</i> BioID proteomic approach, we found Ezrin, the most abundant astrocytic ERM protein, interacts with the Autophagy-Related 7 (Atg7), a master regulator of catabolic processes. The Ezrin/Atg7 interaction is inhibited by Ezrin phosphorylation, thus diminished in the LRRK2 G2019S astrocytes. Importantly, Atg7 function is required to maintain proper astrocyte morphology. These studies reveal an astrocytic molecular mechanism that could serve as a therapeutic target in PD.</p>","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89020817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Geschichte heilen: Urbane Interventionen und ihre Deutung durch den päpstlichen Hofarchitekten Domenico Fontana (1543–1607)","authors":"Fabian Voss","doi":"10.1515/anab-2023-0007","DOIUrl":"https://doi.org/10.1515/anab-2023-0007","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"69 1","pages":"117 - 146"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67253655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"L’amico, la moneta e l’Imperatore: Petrarca tra politica e restaurazione dell’antichità","authors":"P. Rigo","doi":"10.1515/anab-2023-0004","DOIUrl":"https://doi.org/10.1515/anab-2023-0004","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"69 1","pages":"58 - 75"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43395637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Die maiestas als Antitugend? Zur Performanz der herrscherlichen persona in Giovanni Pontanos De principe","authors":"Tristan Spillmann","doi":"10.1515/anab-2023-0005","DOIUrl":"https://doi.org/10.1515/anab-2023-0005","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"69 1","pages":"76 - 99"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43256646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dekolonialisierung und Diversifizierung des Wissens von der Antike: Zur Debatte um ‹Antike und Identität› in den Altertumswissenschaften","authors":"Quintus Immisch, Saskia Schomber","doi":"10.1515/anab-2023-0002","DOIUrl":"https://doi.org/10.1515/anab-2023-0002","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"69 1","pages":"21 - 43"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47358368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"La Tebe di Stazio come figura della civitas diaboli nella Commedia di Dante","authors":"Maria Maślanka-Soro","doi":"10.1515/anab-2023-0003","DOIUrl":"https://doi.org/10.1515/anab-2023-0003","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"69 1","pages":"44 - 57"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48782533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ψεύσματα ποικίλα: Lukians Wahre Geschichten und Amerigo Vespuccis Berichte aus der Neuen Welt","authors":"Katharina Wesselmann","doi":"10.1515/anab-2023-0006","DOIUrl":"https://doi.org/10.1515/anab-2023-0006","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"69 1","pages":"100 - 116"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49574763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"«May our journey be long, filled with agony and torment» – Transformierte mythologische Stoffe und Motive in Louis Leterriers Clash of the Titans (2010)","authors":"Laura Frölich","doi":"10.1515/anab-2023-0009","DOIUrl":"https://doi.org/10.1515/anab-2023-0009","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"69 1","pages":"170 - 190"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45406443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antike im Plural Deutsche Altertumskonkurrenzen im 19. und frühen 20. Jahrhundert","authors":"Andrea Polaschegg","doi":"10.1515/anab-2023-0001","DOIUrl":"https://doi.org/10.1515/anab-2023-0001","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"69 1","pages":"1 - 20"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46188033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-22DOI: 10.1515/anab-2023-frontmatter1
{"title":"Titelseiten","authors":"","doi":"10.1515/anab-2023-frontmatter1","DOIUrl":"https://doi.org/10.1515/anab-2023-frontmatter1","url":null,"abstract":"","PeriodicalId":42033,"journal":{"name":"ANTIKE UND ABENDLAND","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135716561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"历史学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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