Abstract
Mutant ubiquitin (UBB+1), a product of "molecular misreading," is toxic to cells because its ubiquitinated form inhibits the proteasome, contributing to accumulation of misfolded proteins and their ensuing toxicity. The authors demonstrate in 10 sporadic inclusion body myositis (s-IBM) muscle biopsies that UBB+1 is accumulated in aggregates containing amyloid-beta and phosphorylated-tau. In s-IBM, UBB+1 may be pathogenic by inhibiting proteasome, thereby promoting accumulation of cytotoxic misfolded amyloid-beta and phosphorylated-tau.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Amyloid beta-Peptides / metabolism
-
Biopsy
-
Humans
-
Microscopy, Fluorescence
-
Microscopy, Immunoelectron
-
Molecular Sequence Data
-
Muscle Fibers, Skeletal / metabolism*
-
Muscular Diseases / metabolism
-
Muscular Diseases / pathology
-
Myositis, Inclusion Body / genetics*
-
Myositis, Inclusion Body / metabolism
-
Myositis, Inclusion Body / pathology
-
Phosphorylation
-
Proteasome Inhibitors
-
Protein Folding
-
Protein Processing, Post-Translational
-
Ubiquitin / genetics*
-
Ubiquitin / metabolism
-
tau Proteins / metabolism
Substances
-
Amyloid beta-Peptides
-
Proteasome Inhibitors
-
UBB protein, human
-
Ubiquitin
-
tau Proteins