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 Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Increased levels of nicotinamide/nicotinic acid mononucleotide adenylyltransferase ( NMNAT ) act as a powerful suppressor of Wallerian degeneration and ataxin- and tau-induced neurodegeneration in flies and mice. However, the nature of the suppression mechanism/s remains controversial. Here, we show that in yeast models of proteinopathies, overexpression of the  NMNAT  yeast homologs,  NMA1 and NMA2 , suppresses polyglutamine (PolyQ) and α-synuclein-induced cytotoxicities. Unexpectedly, overexpression of other genes in the salvage pathway for NAD +  biosynthesis, including  QNS1 ,  NPT1  and  PNC1  also protected against proteotoxicity. Our data revealed that in all cases, this mechanism involves extensive clearance of the non-native protein. Importantly, we demonstrate that suppression by  NMA1  does not require the presence of a functional salvage pathway for NAD +  biosynthesis,  SIR2  or an active mitochondrial oxidative phosphorylation (OXPHOS) system. Our results imply the existence of histone deacetylase- and OXPHOS-independent crosstalk between the proteins in the salvage pathway for NAD +  biosynthesis and the proteasome that can be manipulated to achieve cellular protection against proteotoxic stress.

human molecular genetics

NAD +  salvage pathway proteins suppress proteotoxicity in yeast models of neurodegeneration by promoting the clearance of misfolded/oligomerized proteins