Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: 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; Jerre van Veluw, G; Hofstra, Robert M W; Rubinsztein, David C; Nollen, Ellen A A
Year of Publication: 2010
Journal: Cell
Volume: 142
Issue: 4
Pagination: 601-12
Date Published: 08/2010
Publication Language: eng
ISSN: 1097-4172
Keywords: alpha-Synuclein, Amyloid beta-Peptides, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Aging, Cell Line, Cell Line, Tumor, Humans, Mice, Nerve Tissue Proteins, Neurodegenerative Diseases, Peptides, Proteins

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.

DOI: 10.1016/j.cell.2010.07.020
Alternate Journal: Cell