Publication

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

van Ham, T. J., Holmberg, M. A., van der Goot, A. T., Teuling, E., Garcia-Arencibia, M., Kim, H., Du, D., Thijssen, K. L., Wiersma, M., Burggraaff, R., van Bergeijk, P., van Rheenen, J., Jerre van Veluw, G., Hofstra, R. M. W., Rubinsztein, D. C. & Nollen, E. A. A., 20-Aug-2010, In : Cell. 142, 4, p. 601-12 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Tjakko J van Ham
  • 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

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.

Original languageEnglish
Pages (from-to)601-12
Number of pages12
JournalCell
Volume142
Issue number4
Publication statusPublished - 20-Aug-2010

    Keywords

  • 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, alpha-Synuclein

ID: 19535622