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The enteric nervous system in PD: gateway, bystander victim, or source of solutions

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Abstract

Apart from the characteristic and progressive motor- and movement-related problems, Parkinson’s disease (PD) patients also suffer from several non-motor symptoms, including gastrointestinal dysfunction. The fact that the enteric nervous system (ENS) controls motility and that one of the typical PD hallmarks, α-synuclein-positive deposits, has also been found in the intestinal wall have rendered the ENS and the gut a popular subject of study in the context of PD. The possibility that these deposits could serve as an early biomarker is obviously of tremendous medical benefit but also the idea that the gut may possibly be a gateway via which the disease is initiated and progressively makes its way via the peripheral nerves to the central nervous system has increased the interest in the ENS–PD link. Furthermore, the fact that gastrointestinal symptoms are present in PD suggests that the ENS might be affected as well. However, despite a large body of literature on the topic, the actual role or the magnitude of involvement of the ENS in PD remains elusive. The multitudes of experimental approaches and animal models have complicated the interpretation of results and the outcome of different studies does not necessarily align well. In this review, we chose to highlight some elements of interest and some items of confusion, particularly those where research should be focusing. We also list a number of open questions in the field that could serve as a guideline for future, preferably concerted research.

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Abbreviations

AS:

α-Synuclein

α-synGFP:

α-Synuclein green fluorescent protein

CNS:

Central nervous system

BAC:

Bacterial artificial chromosome

DAT:

Dopamine transporter

DBH:

Dopamine β-hydroxylase

D2:

Dopamine receptor subtype 2

DMV:

Dorsal motor nucleus of the vagus nerve

ENS:

Enteric nervous system

GI:

Gastrointestinal

h-AS:

Human α-synuclein

IBD:

Inflammatory bowel disease

kD:

Kilodalton

P-AS:

Phosphorylated α-synuclein

PD:

Parkinson’s Disease

P-specific:

Phosphorylated specific

NFM:

Neurofilament M (medium)

SN:

Substantia nigra

SNARE:

Soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor

TH:

Tyrosine hydroxylase

Thy1-AS:

Thy1 promoter induced α-synuclein

VIP:

Vasointestinal peptide

WT:

Wild type

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FWO – G.0A44.13 (PVB)

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Authors and Affiliations

  1. UW School of Medicine and Public Health, Madison, WI, USA

    Kathleen Shannon

  2. Lab. for Enteric NeuroScience (LENS), Translational Research of Gastrointestinal Disorder (TARGID), CHROMETA, University of Leuven, Leuven, Belgium

    Pieter Vanden Berghe

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  1. Kathleen Shannon
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  2. Pieter Vanden Berghe
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Correspondence to Pieter Vanden Berghe.

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Shannon, K., Vanden Berghe, P. The enteric nervous system in PD: gateway, bystander victim, or source of solutions. Cell Tissue Res 373, 313–326 (2018). https://doi.org/10.1007/s00441-018-2856-4

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  • DOI: https://doi.org/10.1007/s00441-018-2856-4

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