{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Barmada SJ"],"funding":["NIMH NIH HHS","NINDS NIH HHS","Motor Neurone Disease Association"],"pagination":["677-85"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4106236"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(8)"],"pubmed_abstract":["Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology--cytoplasmic inclusions rich in transactive response element DNA-binding protein of 43 kDa (TDP43). Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause disease even if TDP43 lacks a mutation. Here we show that individual neurons vary in their ability to clear TDP43 and are exquisitely sensitive to TDP43 levels. To measure TDP43 clearance, we developed and validated a single-cell optical method that overcomes the confounding effects of aggregation and toxicity and discovered that pathogenic mutations shorten TDP43 half-life. New compounds that stimulate autophagy improved TDP43 clearance and localization and enhanced survival in"],"journal":["Nature chemical biology"],"pubmed_title":["Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models."],"pmcid":["PMC4106236"],"funding_grant_id":["U24 NS078370","R43 NS081844","CHANDRAN/MAR10/982-797","K08 NS072233","R01 NS083390","U01 MH1050135","3R01 NS039074","U01 MH105035","R01 NS039074"],"pubmed_authors":["Bilican B","Peisach D","Shaw C","Tsvetkov A","Barmada SJ","Ando DM","Serio A","Li X","Finkbeiner S","Arjun A","Pleiss M","Daub A","Chandran S"],"additional_accession":[]},"is_claimable":false,"name":"Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models.","description":"Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology--cytoplasmic inclusions rich in transactive response element DNA-binding protein of 43 kDa (TDP43). Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause disease even if TDP43 lacks a mutation. Here we show that individual neurons vary in their ability to clear TDP43 and are exquisitely sensitive to TDP43 levels. To measure TDP43 clearance, we developed and validated a single-cell optical method that overcomes the confounding effects of aggregation and toxicity and discovered that pathogenic mutations shorten TDP43 half-life. New compounds that stimulate autophagy improved TDP43 clearance and localization and enhanced survival in","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Aug","modification":"2025-04-19T04:16:11.103Z","creation":"2019-03-27T01:32:31Z"},"accession":"S-EPMC4106236","cross_references":{"pubmed":["24974230"],"doi":["10.1038/nchembio.1563"]}}