Prion-like propagation of α-synuclein in the gut-brain axis

Abstract

Parkinson's disease (PD) is a progressive degenerative disease of the nervous system, which is characterized by movement disorders, such as static tremor, rigidity, and bradykinesia in advanced patients. Gastrointestinal (GI) dysfunction, such as gastric dysmotility, constipation, and anorectic dysfunction, is common non-motor symptom in the early stage of PD. The progression of PD includes the degenerative loss of dopaminergic (DA) neurons and aggregation of α-synuclein in the substantia nigra (SN). Interestingly, both of them are also present in the enteric nervous system (ENS) of PD patients. In this review, we describe the relationship between non-motor symptoms particularly GI dysfunction and the pathogenesis of PD, aiming to show the powerful evidences about the prion-like propagation of α-synuclein and support the hypothesis of gut-brain axis in PD. We then summarize the mechanism of the gut-brain axis and confirm α-synuclein as a potential target for drug design or new clinical treatment.

Keywords: Enteric nervous system; Gut-brain axis; Non-motor symptom; Parkinson’s disease; Prion-like; α-synuclein.