Multifaceted Influences of Melanin-Like Particles on Amyloid-beta Aggregation

Abstract

The properties of eumelanin-like particles (EMPs) and pheomelanin-like particles (PMPs) in regulating the process of amyloid formation of amyloid-beta 42 (A beta 42) were examined. EMPs and PMPs are effective both in interfering with amyloid aggregation of A beta 42 and in remodeling matured Alpha beta 42 fibers. The results suggest that some (but not all) molecular species consisting of melanin-like particles (MPs) are responsible for their inhibiting property toward amyloid formation, and the influence is likely manifested by long-range interactions. Incubating preformed A beta 42 fibers with catechols or MPs leads to the formation of mesh-like, interconnected A beta 42 fibers encapsulated with melanin-like material. MPs are kinetically more effective than catechol monomers in this process, and a detailed investigation reveals that 4,5-dihydroxyindole, a major intermediate in the formation of melanin-like species, and its derivatives are mainly responsible for remodeling amyloid fibers.