Gut microbiota: a potential therapeutic target for Parkinson's disease

José Fidel Baizabal-Carvallo

摘要：Parkinson's disease (PD) is a neurodegenerative disorder characterized by accumulation of α-synuclein in neurons of the central nervous system (CNS). The pathogenesis of PD is complex and only partially understood. Initial evidence pointed to the basal ganglia as the source of the motor manifestations of PD, and likely the origin of the pathological process. In the last two decades, Braak and colleagues have drawn attention to the presence of α-synuclein in the nuclei of lower cranial nerves, suggesting that such protein was transported from somewhere in the gut. This finding started shifting the focus from the CNS to the gut in search for a pathogenic explanation for PD. Further pathological studies confirmed the presence of aggregated α-synuclein in the gut of individuals with PD. However, later observations showed that such abnormality was also present in some individuals without PD. These observations suggested that α-synuclein aggregates may be related to an infectious agent affecting the gut epithelia. In this scenario, gut microbiota may contribute to aggregation of α-synuclein. Emerging evidence has shown that protein nucleation and aggregation may be influenced by an extracellular amyloid protein called "curli", secreted by E Coli. Indeed, repeated administration of curli-producing bacteria to Caenorhabditis elegans and rats has induced neuronal deposition of α-synuclein in their gut and CNS promoting local inflammation (Chen et al., 2016).