The peripheral component of neurodegeneration: uptake and transmission of amyloid proteins in the enteric nervous system.

Since a few years, evidence is growing that a disease process affecting the central nervous system (CNS) can also involve its enteric counterpart (ENS) and vice-versa. Indeed, various neurodegenerative disorders are accompanied or even preceded by gastrointestinal malfunctions. This relationship is well-documented for prion diseases and Parkinson's disease, but has not yet been scrutinized for Alzheimer's disease (AD), a devastating neurodegenerative disorder that is typified by a progressive and debilitating cognitive decline. A defining feature of AD is the accumulation of misfolded amyloid-beta peptides. Considering that the CNS and ENS are highly interconnected, the gut microbiome produces amyloids that can cross-seed polymerization, and inflammation promotes amyloid build-up, it is highly conceivable that the gut is a vulnerable node for amyloid-driven degeneration. Yet, the mechanisms underlying cellular processing of amyloids in the ENS are poorly characterized. Hence, with this research project, we will investigate the entry routes, spreading behaviour and cellular effects of microbial and host-derived amyloid proteins in the ENS. Using innovative imaging technologies and well-defined molecular characterization methods, this work will provide a solid basis for refining the gut-brain axis theory in the context of AD and will open novel avenues for both fundamental and clinical research with relevance for a broad range of proteopathic neurodegenerative diseases.

Keywords:AGEING PROCES, ENTERIC NERVOUS SYSTEM, INFLAMMATION, AMYLOID PROTEIN

Disciplines:Animal cell and molecular biology, Animal morphology, anatomy and physiology, Gastro-enterology, Neuroanatomy, Neurological and neuromuscular diseases, Neurophysiology, Neuroimaging