{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vest RT"],"funding":["Life Sciences Research Foundation","Michael J. Fox Foundation for Parkinson''''s Research","NIA NIH HHS","Glenn Foundation for Medical Research","HHS | NIH | National Institute of Neurological Disorders and Stroke","NINDS NIH HHS","HHS | NIH | National Institute on Aging"],"pagination":["e2121609119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8931323"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(11)"],"pubmed_abstract":["SignificanceNeurodegenerative diseases are poorly understood and difficult to treat. One common hallmark is lysosomal dysfunction leading to the accumulation of aggregates and other undegradable materials, which cause damage to brain resident cells. Lysosomes are acidic organelles responsible for breaking down biomolecules and recycling their constitutive parts. In this work, we find that the antiinflammatory and neuroprotective compound, discovered via a phenotypic screen, imparts its beneficial effects by targeting the lysosome and restoring its function. This is established using a genome-wide CRISPRi target identification screen and then confirmed using a variety of lysosome-targeted studies. The resulting small molecule from this study represents a potential treatment for neurodegener"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Small molecule C381 targets the lysosome to reduce inflammation and ameliorate disease in models of neurodegeneration."],"pmcid":["PMC8931323"],"funding_grant_id":["AG054407","NS092868","P01 AG054407","U01 NS057496","RF1 AG059694","NS057496","R01 NS092868","fellowship","grant","RF1 AG064897","ASAP"],"pubmed_authors":["Shuken S","Zhang H","Green C","Tanga M","Vest RT","Laqtom NN","Bassik MC","Li L","Frydman J","Yang AC","Wyss-Coray T","Haney MS","Chang B","Luo J","Nguyen A","Chou CC","Yerra L","Abu-Remaileh M"],"additional_accession":[]},"is_claimable":false,"name":"Small molecule C381 targets the lysosome to reduce inflammation and ameliorate disease in models of neurodegeneration.","description":"SignificanceNeurodegenerative diseases are poorly understood and difficult to treat. One common hallmark is lysosomal dysfunction leading to the accumulation of aggregates and other undegradable materials, which cause damage to brain resident cells. Lysosomes are acidic organelles responsible for breaking down biomolecules and recycling their constitutive parts. In this work, we find that the antiinflammatory and neuroprotective compound, discovered via a phenotypic screen, imparts its beneficial effects by targeting the lysosome and restoring its function. This is established using a genome-wide CRISPRi target identification screen and then confirmed using a variety of lysosome-targeted studies. The resulting small molecule from this study represents a potential treatment for neurodegener","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2025-04-22T07:47:51.648Z","creation":"2024-11-13T17:18:31.264Z"},"accession":"S-EPMC8931323","cross_references":{"pubmed":["35259016"],"doi":["10.1073/pnas.2121609119"]}}