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All of the disease-associated TDP-43 mutants tested have been shown to increase TDP-43 half-life and this correlates inversely with the age at which the sufferer first becomes aware of symptoms. Here we show that disease mutations in two TDP-43 nucleic acid binding domains also increase the protein\u2019s half-life and this is commensurate with increased structural stability and resistance to aggregation. Our results are an unusual contrast to other neurodegenerative diseases and provide a potential link between the molecular characteristics of mutant TDP-43 and the symptoms of these debilitating diseases.<\/jats:p>","DOI":"10.1073\/pnas.1317317111","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T21:26:27Z","timestamp":1393881987000},"page":"4309-4314","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":83,"title":["Disease causing mutants of TDP-43 nucleic acid binding domains are resistant to aggregation and have increased stability and half-life"],"prefix":"10.1073","volume":"111","author":[{"given":"James A.","family":"Austin","sequence":"first","affiliation":[{"name":"Molecular Biophysics Group, Institute of Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth S. 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