Discovery and characterization of a mammalian amyloid disaggregation activity

Abstract

The formation of amyloid, a cross‐β‐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 β (Aβ)_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.