Format

Send to

Choose Destination
JCI Insight. 2017 Jun 15;2(12). pii: 92295. doi: 10.1172/jci.insight.92295. [Epub ahead of print]

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

Author information

1
Department of Medicine, Duke University and Durham VA Medical Centers, Durham, North Carolina, USA.
2
Department of Pathology and.
3
Department of Medicine, UCSF, San Francisco, California, USA.
4
Invitae Corporation, San Francisco, California, USA.
5
Duke Institute for Brain Sciences, Durham, North Carolina, USA.

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 α-synuclein known as Lewy bodies. Although the cause of sporadic PD is not well understood, abundant clinical and pathological evidence show that misfolded α-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 α-synuclein initiates misfolding of native α-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 α-synuclein is expressed in the EEC line, STC-1, and native EECs of mouse and human intestine. Furthermore, α-synuclein-containing EECs directly connect to α-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 α-synuclein folding in the EECs, thereby beginning a process by which misfolded α-synuclein could propagate from the gut epithelium to the brain.

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center