The role of microbial amyloid in neurodegeneration

Abstract

It has become apparent that the intestinal microbiota orchestrates important aspects of our metabolism, immunity, and development. Recent work has demonstrated that the microbiota also influences brain function in healthy and diseased individuals. Of great interest are reports that intestinal bacteria play a role in the pathogenic cascade of both Parkinson and Alzheimer diseases. These neurodegenerative disorders both involve misfolding of endogenous proteins that spreads from one region of the body to another in a manner analogous to prions. The mechanisms of how the microbiota influences or is correlated with disease require elaboration. Microbial proteins or metabolites may influence neurodegeneration through the promotion of amyloid formation by human proteins or by enhancing inflammatory responses to endogenous neuronal amyloids. We review the current knowledge concerning bacterial amyloids and their potential to influence cerebral amyloid aggregation and neuroinflammation. We propose the term “mapranosis” to describe the process of microbiota-associated proteopathy and neuroinflammation. The study of amyloid proteins made by the microbiota and their influence on health and disease is in its infancy. This is a promising area for therapeutic intervention because there are many ways to alter our microbial partners and their products, including amyloid proteins.