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

Publication ,  Journal Article
Chandra, R; Hiniker, A; Kuo, Y-M; Nussbaum, RL; Liddle, RA
Published in: JCI Insight
June 15, 2017

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.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

June 15, 2017

Volume

2

Issue

12

Location

United States

Related Subject Headings

  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Chandra, R., Hiniker, A., Kuo, Y.-M., Nussbaum, R. L., & Liddle, R. A. (2017). α-Synuclein in gut endocrine cells and its implications for Parkinson's disease. JCI Insight, 2(12). https://doi.org/10.1172/jci.insight.92295
Chandra, Rashmi, Annie Hiniker, Yien-Ming Kuo, Robert L. Nussbaum, and Rodger A. Liddle. “α-Synuclein in gut endocrine cells and its implications for Parkinson's disease.JCI Insight 2, no. 12 (June 15, 2017). https://doi.org/10.1172/jci.insight.92295.
Chandra R, Hiniker A, Kuo Y-M, Nussbaum RL, Liddle RA. α-Synuclein in gut endocrine cells and its implications for Parkinson's disease. JCI Insight. 2017 Jun 15;2(12).
Chandra, Rashmi, et al. “α-Synuclein in gut endocrine cells and its implications for Parkinson's disease.JCI Insight, vol. 2, no. 12, June 2017. Pubmed, doi:10.1172/jci.insight.92295.
Chandra R, Hiniker A, Kuo Y-M, Nussbaum RL, Liddle RA. α-Synuclein in gut endocrine cells and its implications for Parkinson's disease. JCI Insight. 2017 Jun 15;2(12).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

June 15, 2017

Volume

2

Issue

12

Location

United States

Related Subject Headings

  • 42 Health sciences
  • 32 Biomedical and clinical sciences