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The study investigates how this mutation affects GTPase activity and downstream cellular processes using an in-vitro PD model. Rapamycin combined with methyl 2-hydroxybenzoate (methyl salicylate) is tested to restore hydrolysis, regulate mTORC1 signaling, improve autophagic fluidity, and reduce neurodegenerative features. Outcomes are evaluated through viability, GTPase activity, ROS, caspase, ELISA, and knockdown plus fluorescence microscopy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/synergistic-modulation-of-gtpase-hydrolysis-and-mtorc1-activity-in-lrrk2-g2019s-parkinsons-disease/428180/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/synergistic-modulation-of-gtpase-hydrolysis-and-mtorc1-activity-in-lrrk2-g2019s-parkinsons-disease/428180.png","ImageObject",300,407,{"name":92,"@type":93},"Cart","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-06","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does the LRRK2-G2019S mutation play in Parkinson’s disease within this study?","Question",{"text":112,"@type":113},"The study states that LRRK2-G2019S mutation is implicated in dysregulating GTPase hydrolysis, which impacts mTORC1 signaling in Parkinson’s disease.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What treatment combination is hypothesized to correct the pathway, and what effects are expected?",{"text":117,"@type":113},"It hypothesizes Rapamycin (an mTORC1 inhibitor) combined with methyl 2-hydroxybenzoate (methyl salicylate), expected to restore GTPase hydrolysis, regulate mTORC1 signaling, mitigate autophagic fluidity issues, and reduce oxidative stress and apoptosis markers.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the study plan to measure cellular changes and mechanism-related outcomes?",{"text":121,"@type":113},"It plans to use MTS-based viability, fluorescence-based GTPase activity assays, ROS-Glo, Caspase-Glo 9, ELISA for cell health, and knockdown plus fluorescence microscopy to visualize mTORC1 activity responses.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},428180,1790772520,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":8,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":81},18829141979164,"https://eur-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","1148 Innovation in Aging, 2025, Vol. 9, No. S2  \nAbstract citation ID: igaf122.3848  \nSYNERGISTIC MODULATION OF GTPASE HYDROLYSIS  \nAND MTORC1 ACTIVITY IN LRRK2-G2019S  \nPARKINSON’S DISEASE  \nZainab Cheema,“Bergen County Academies”, Maywood, New Jersey, United States  \nThe LRRK2-G2019S mutation is implicated in the dysregulation of GTPase hydrolysis activity, which affects the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway in Parkinson’s disease (PD) . This study aims to investigate how this mutation influences GTPase activity and its downstream effects on cellular processes in an in-vitro model of Parkinson’s Disease. It is hypothesized that treatment with Rapamycin, an mTORC1 inhibitor, in combination with Methyl 2-Hydroxybenzoate (Methyl Salicylate), a small molecule targeting GTPases, will restore GTPase hydrolysis activity, mitigate autophagic fluidity, regulate mTORC1 signaling, and reduce neurodegenerative features. Additionally, the treatment is expected to decrease reactive oxygen species (ROS) accumulation and apoptosis markers, promoting cell survival by preventing oxidative damage. Experimental techniques include MTS-based cell viability, Fluorescence-based GTPase activity, ROS-Glo, Caspase-Glo 9 and enzyme-linked immunosorbent assays (ELISA) analysis to assess changes in cell health, autophagic flux, and GTPase cycling. Genetic knockdown approaches combined with fluorescence microscopy will be used to visualize mTORC1 activity responses. Preliminary findings suggest that targeting GTPase dysfunction in mTORC1 signaling could offer novel therapeutic strategies for PD and broader neurodegenerative disease management, but further data analysis is required to validate these results.","cbCaiuVb6JDOhWa5","https://ap.wps.com/l/cbCaiuVb6JDOhWa5","pdf",1011334,"English","# Abstract\n## Study Rationale\n## Hypothesis and Treatment Plan\n## Experimental Methods\n## Expected Outcomes and Preliminary Implications","[{\"question\":\"What role does the LRRK2-G2019S mutation play in Parkinson’s disease within this study?\",\"answer\":\"The study states that LRRK2-G2019S mutation is implicated in dysregulating GTPase hydrolysis, which impacts mTORC1 signaling in Parkinson’s disease.\"},{\"question\":\"What treatment combination is hypothesized to correct the pathway, and what effects are expected?\",\"answer\":\"It hypothesizes Rapamycin (an mTORC1 inhibitor) combined with methyl 2-hydroxybenzoate (methyl salicylate), expected to restore GTPase hydrolysis, regulate mTORC1 signaling, mitigate autophagic fluidity issues, and reduce oxidative stress and apoptosis markers.\"},{\"question\":\"How does the study plan to measure cellular changes and mechanism-related outcomes?\",\"answer\":\"It plans to use MTS-based viability, fluorescence-based GTPase activity assays, ROS-Glo, Caspase-Glo 9, ELISA for cell health, and knockdown plus fluorescence microscopy to visualize mTORC1 activity responses.\"}]","SYNERGISTIC MODULATION OF GTPASE HYDROLYSIS AND MTORC1 ACTIVITY IN LRRK2-G2019S PARKINSON’S DISEASE | PDF",1790646011]