?-Synuclein in gut endocrine cells and its implications for Parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is a progressive neurodegenerative disease with devastating clinical manifestations. In PD, neuronal death is associated with intracellular aggregates of the neuronal protein ?-synuclein known as Lewy bodies. Although the cause of sporadic PD is not well understood, abundant clinical and pathological evidence show that misfolded ?-synuclein is found in enteric nerves before it appears in the brain. This suggests a model in which PD pathology originates in the gut and spreads to the central nervous system via cell-to-cell prion-like propagation, such that transfer of misfolded ?-synuclein initiates misfolding of native ?-synuclein in recipient cells. We recently discovered that enteroendocrine cells (EECs), which are part of the gut epithelium and directly face the gut lumen, also possess many neuron-like properties and connect to enteric nerves. In this report, we demonstrate that ?-synuclein is expressed in the EEC line, STC-1, and native EECs of mouse and human intestine. Furthermore, ?-synuclein-containing EECs directly connect to ?-synuclein-containing nerves, forming a neural circuit between the gut and the nervous system in which toxins or other environmental influences in the gut lumen could affect ?-synuclein folding in the EECs, thereby beginning a process by which misfolded ?-synuclein could propagate from the gut epithelium to the brain.

SUBMITTER: Chandra R 

PROVIDER: S-EPMC5470880 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other