RRC ID 54285
Author van Ham TJ, Holmberg MA, van der Goot AT, Teuling E, Garcia-Arencibia M, Kim HE, Du D, Thijssen KL, Wiersma M, Burggraaff R, van Bergeijk P, van Rheenen J, Jerre van Veluw G, Hofstra RM, Rubinsztein DC, Nollen EA.
Title Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity.
Journal Cell
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.
Volume 142(4)
Pages 601-12
Published 2010-8-20
DOI 10.1016/j.cell.2010.07.020
PII S0092-8674(10)00789-0
PMID 20723760
MeSH Amyloid beta-Peptides / metabolism Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / metabolism* Cell Line Cell Line, Tumor Cellular Senescence* Humans Mice Nerve Tissue Proteins / chemistry Nerve Tissue Proteins / metabolism* Neurodegenerative Diseases / metabolism* Peptides / metabolism Proteins / chemistry Proteins / metabolism* alpha-Synuclein / metabolism
IF 36.216
Times Cited 58
C.elegans tm4909