Identification of MOAG-4/SERF as a Regulator of Age-Related Proteotoxicity

作者：van Ham Tjakko J; Holmberg Mats A; van der Goot Annemieke T; Teuling Eva; Garcia Arencibia Moises; Kim Hyun eui; Du Deguo; Thijssen Karen L; Wiersma Marit; Burggraaff Rogier; van Bergeijk Petra; van Rheenen Jeroen; van Veluw G Jerre; Hofstra Robert M W; Rubinsztein David C; Nollen Ellen A A^*

来源：Cell, 2010, 142(4): 601-612.

DOI：10.1016/j.cell.2010.07.020

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.

• 出版日期2010-8-20
• 单位河北医科大学