| Literature DB >> 20723760 |
Tjakko J van Ham1, Mats A Holmberg, Annemieke T van der Goot, Eva Teuling, Moises Garcia-Arencibia, Hyun-eui Kim, Deguo Du, Karen L Thijssen, Marit Wiersma, Rogier Burggraaff, Petra van Bergeijk, Jeroen van Rheenen, G Jerre van Veluw, Robert M W Hofstra, David C Rubinsztein, Ellen A A Nollen.
Abstract
Fibrillar 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. Copyright 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20723760 DOI： 10.1016/j.cell.2010.07.020
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582