کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2036772 | 1072281 | 2010 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Identification of MOAG-4/SERF as a Regulator of Age-Related Proteotoxicity Identification of MOAG-4/SERF as a Regulator of Age-Related Proteotoxicity](/preview/png/2036772.png)
SummaryFibrillar protein aggregates are the major pathological hallmark of several incurable, age-related, neurodegenerative disorders. These aggregates typically contain aggregation-prone pathogenic proteins, such as amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's disease. It is, however, poorly understood how these aggregates are formed during cellular aging. Here we identify an evolutionarily highly conserved modifier of aggregation, MOAG-4, as a positive regulator of aggregate formation in C. elegans models for polyglutamine diseases. Inactivation of MOAG-4 suppresses the formation of compact polyglutamine aggregation intermediates that are required for aggregate formation. The role of MOAG-4 in driving aggregation extends to amyloid-beta and alpha-synuclein and is evolutionarily conserved in its human orthologs SERF1A and SERF2. MOAG-4/SERF appears to act independently from HSF-1-induced molecular chaperones, proteasomal degradation, and autophagy. Our results suggest that MOAG-4/SERF regulates age-related proteotoxicity through a previously unexplored pathway, which will open up new avenues for research on age-related, neurodegenerative diseases.
Graphical AbstractFigure optionsDownload high-quality image (159 K)Download as PowerPoint slideHighlights
► MOAG-4 promotes aggregation of aggregation-prone disease proteins
► Inactivation of MOAG-4 suppresses age-related proteotoxicity
► MOAG-4 regulates proteotoxicity independently of HSF-1 and DAF-16
► The role of MOAG-4 is evolutionarily conserved in human SERF1A and SERF2
Journal: - Volume 142, Issue 4, 20 August 2010, Pages 601–612