| First Author | Chandra R | Year | 2017 |
| Journal | JCI Insight | Volume | 2 |
| Issue | 12 | PubMed ID | 28614796 |
| Mgi Jnum | J:344231 | Mgi Id | MGI:7574271 |
| Doi | 10.1172/jci.insight.92295 | Citation | Chandra R, et al. (2017) alpha-Synuclein in gut endocrine cells and its implications for Parkinson's disease. JCI Insight 2(12):e92295 |
| abstractText | 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. |
