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We have previously demonstrated the cytoplasmic aggregate formation of adenovirally expressed transactivation response DNA\u2010binding protein of 43\u2009kDa (TDP\u201043), the main constituent of neuronal cytoplasmic aggregates in cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), in cultured neuronal cells under the condition of proteasome inhibition. The TDP\u201043 aggregate formation was markedly suppressed by co\u2010infection of adenoviruses expressing heat shock transcription factor 1 (HSF1), a master regulator of heat shock response, and Praja1 RING\u2010finger E3 ubiquitin ligase (PJA1) located downstream of the HSF1 pathway. In the present study, we examined other reportedly known E3 ubiquitin ligases for TDP\u201043, i.e. Parkin, RNF112 and RNF220, but failed to find their suppressive effects on neuronal cytoplasmic TDP\u201043 aggregate formation, although they all bind to TDP\u201043 as verified by co\u2010immunoprecipitation. In contrast, PJA1 also binds to adenovirally expressed wild\u2010type and mutated fused in sarcoma, superoxide dismutase 1, \u03b1\u2010synuclein and ataxin\u20103, and huntingtin polyglutamine proteins in neuronal cultures and suppressed the aggregate formation of these proteins. These results suggest that PJA1 is a common sensing factor for aggregate\u2010prone proteins to counteract their aggregation propensity, and could be a potential therapeutic target for neurodegenerative diseases that include ALS, FTLD, Parkinson's disease and polyglutamine diseases.<\/jats:p>","DOI":"10.1111\/neup.12840","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T04:55:55Z","timestamp":1655268955000},"page":"488-504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Praja1 <scp>RING<\/scp>\u2010finger <scp>E3<\/scp> ubiquitin ligase is a common suppressor of neurodegenerative disease\u2010associated protein aggregation"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0245-3834","authenticated-orcid":false,"given":"Kazuhiko","family":"Watabe","sequence":"first","affiliation":[{"name":"Department of Medical Technology (Neuropathology), 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