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

The properties of eumelanin-like particles (EMPs) and pheomelanin-like particles (PMPs) in regulating the process of amyloid formation of amyloid-beta 42 (Aβ42) were examined. EMPs and PMPs are effective both in interfering with amyloid aggregation of Aβ42 and in remodeling matured Αβ42 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 Aβ42 fibers with catechols or MPs leads to the formation of mesh-like, interconnected Aβ42 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.