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.
journal_name
Celljournal_title
Cellauthors
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 EAdoi
10.1016/j.cell.2010.07.020subject
Has Abstractpub_date
2010-08-20 00:00:00pages
601-12issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(10)00789-0journal_volume
142pub_type
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