Structural Mimicry in Microbial and Antimicrobial Amyloids Connected to Neurodegenerative Diseases

Mounting evidence indicates the causal relationship between microbes and neurodegenerative diseases via several potential pathways; some involve amyloids, proteins that self-assemble into unique supramolecular fibers. A remarkable variety of microbial species of human pathogens and microbiome generates significant quantities of secreted amyloids utilized to facilitate multicellular and pathogenic behaviors. This project will explicitly evaluate the hypothesis that microbial amyloids could trigger human amyloids in a pathological process reminiscent of diseases transmittable by prion-contaminated meat. In addition, we will clarify, at the protein structure level, the connection between amyloids and antimicrobial and immunomodulating activities, underlining a potential role of human amyloids reacting to microbial infections as part of neuroimmunity, which can, after many years, turn pathogenic to the brain. Owing to the revolution in resolution and advances in correlative cryogenic light and electron microscopy, we foresee high-resolution (nanometric to atomic) visualization of brain sections of neurodegeneration patients with a medical history of severe infections or abnormal microbiome. Such information would enable the development of prevention and therapeutic strategies for neurodegeneration.