Title | Discovery and characterization of a mammalian amyloid disaggregation activity. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Murray AN, Solomon JP, Wang Y-J, Balch WE, Kelly JW |
Journal | Protein Sci |
Volume | 19 |
Issue | 4 |
Pagination | 836-46 |
Date Published | 2010 Apr |
ISSN | 1469-896X |
Keywords | Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Cells, Cultured, Humans, Hydrogen-Ion Concentration, Mice, Microscopy, Atomic Force, Peptide Fragments, Protease Nexins, Protein Multimerization, Receptors, Cell Surface, Temperature |
Abstract | The formation of amyloid, a cross-beta-sheet fibrillar aggregate, is associated with a variety of aging-associated degenerative diseases. Herein, we report the existence of a mammalian amyloid disaggregase activity that is present in all tissues and cell types tested. Homogenates from mammalian tissues and cell lines are able to disaggregate amyloid fibrils composed of amyloid beta (A beta)(1-40) or the 8 kDa plasma gelsolin fragment. The mammalian disaggregase activity is sensitive to proteinase K digestion and can be uncoupled from proteolysis activity using a protease inhibitor cocktail. Amyloid disaggregation and proteolysis activities are remarkably resistant to changes in temperature and pH. Identification and manipulation of the proteins responsible for the amyloid disaggregation/degradation activities offers the possibility of ameliorating aggregation-associated diseases. |
DOI | 10.1002/pro.363 |
Alternate Journal | Protein Sci |
PubMed ID | 20162625 |
Grant List | AG031097 / AG / NIA NIH HHS / United States |
Related Faculty:
James Solomon, M.D., Ph.D.