Aberrant action of amyloidogenic host defense peptides: a new paradigm to investigate neurodegenerative disorders?

Host defense peptides (HDPs) are components of the innate immune system with activity against a broad range of microbes. In some cases, it appears that this activity is mediated by the ability of these peptides to permeabilize microbial membranes via the formation of amyloid associated structures. Recent evidence suggests that the naturally occurring function of the Aβ40 and Aβ42 peptides, which are causative agents of Alzheimer's disease, may be to serve as amyloidogenic HDPs. Here, it is hypothesized that the neurotoxicity of these peptides is related to aberrant use of their amyloid-mediated antimicrobial mechanisms, which provides the as yet unexplored paradigm of a relationship among HDPs, neurodegenerative disorders, and other conditions that could contribute to their understanding and remediation.