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Enteric synucleinopathy: from trendy concept to real entity.

Adrien de Guilhem de Lataillade1,2, Thibaud Lebouvier3, Wendy Noble4

  • 1Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France.

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|June 7, 2023
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Summary

Parkinson's disease (PD) involves the gut-brain axis, with alpha-synuclein deposits in the enteric nervous system suggesting a role in PD initiation. This research supports pathological alpha-synuclein in the gut for PD patients.

Keywords:
AggregatesAlpha-synucleinEnteric nervous systemParkinson’s diseaseSynucleinopathiesTauopathies

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Area of Science:

  • Neuroscience
  • Gastroenterology
  • Pathology

Background:

  • Parkinson's disease (PD) is increasingly recognized as affecting the gastrointestinal tract and the gut-brain axis.
  • Alpha-synuclein deposits, the hallmark of PD, are found in the enteric nervous system of nearly all PD patients.
  • The concept of 'enteric synucleinopathy' proposes the enteric nervous system's role in PD initiation and progression.

Purpose of the Study:

  • To compare the physiological and pathophysiological properties of alpha-synuclein in the brain and enteric nervous system.
  • To evaluate the hypothesis that the enteric nervous system plays a pivotal role in PD pathogenesis.
  • To discuss the relevance of gut-brain interactions in other neurodegenerative disorders.

Main Methods:

  • Literature review and synthesis of existing research.
  • Comparative analysis of alpha-synuclein properties in the central and enteric nervous systems.
  • Discussion of current hypotheses and pending questions regarding PD pathogenesis.

Main Results:

  • Accumulating evidence supports the presence of pathological alpha-synuclein species in the gut of Parkinson's disease patients.
  • Gastrointestinal symptoms are nearly universal in PD patients.
  • Autopsy studies consistently reveal alpha-synuclein deposits in the enteric nervous system.

Conclusions:

  • The data strongly support the existence of pathological alpha-synuclein in the gut, consistent with 'enteric synucleinopathy'.
  • The gut-brain axis and enteric nervous system are critical areas for understanding PD initiation and spread.
  • Gut-brain interactions may be significant in other neurodegenerative conditions beyond PD.