English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Transactivation response DNA‐binding protein of 43 kDa (TDP‐43) is a major constituent of cytoplasmic aggregates in neuronal and glial cells in cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We have previously shown neuronal cytoplasmic aggregate formation induced by recombinant adenoviruses expressing human wild‐type and C‐terminal fragment (CTF) TDP‐43 under the condition of proteasome inhibition  in vitro  and  in vivo . In the present study, we demonstrated that the formation of the adenoviral TDP‐43 aggregates was markedly suppressed in rat neural stem cell‐derived neuronal cells by co‐infection of an adenovirus expressing heat shock transcription factor 1 (HSF1), a master regulator of heat shock response. We performed DNA microarray analysis and searched several candidate molecules, located downstream of HSF1, which counteract TDP‐43 aggregate formation. Among these, we identified Praja 1 RING‐finger E3 ubiquitin ligase (PJA1) as a suppressor of phosphorylation and aggregate formation of TDP‐43. Co‐immunoprecipitation assay revealed that PJA1 binds to CTF TDP‐43 and the E2‐conjugating enzyme UBE2E3. PJA1 also suppressed formation of cytoplasmic phosphorylated TDP‐43 aggregates in mouse facial motor neurons  in vivo . Furthermore, phosphorylated TDP‐43 aggregates were detected in PJA1‐immunoreactive human ALS motor neurons. These results indicate that PJA1 is one of the principal E3 ubiquitin ligases for TDP‐43 to counteract its aggregation propensity and could be a potential therapeutic target for ALS and FTLD.

Praja1 RING ‐finger E3 ubiquitin ligase suppresses neuronal cytoplasmic TDP ‐43 aggregate formation