Parallel manifestations of neuropathologies in the enteric and central nervous systems

G. Natale, L. Pasquali, A. Paparelli, F. Fornai

Research output: Contribution to journalArticlepeer-review


Background Neurodegenerative diseases may extend outside the central nervous system (CNS) and involve the gastrointestinal (GI) tract. The gut would appear to be a pathological marker for neurodegeneration, as well as a site for studying the pathophysiology of neurodegeneration. In fact, both in the ENS and CNS, misfolded proteins are likely to initiate a process of neurodegeneration. For example, the very same protein aggregates can be detected both in the ENS and CNS. In both systems, misfolded proteins are likely to share common cell-to-cell diffusion mechanisms, which may occur through a parallel prion-like diffusion process. Independently from the enteric or central origin, misfolded proteins may proceed along the following steps, they: (i) form aggregates; (ii) are expressed on plasma membrane; (iii) are secreted extracellularly; (iv) are glycated to form advanced glycation end-products (AGEs); (v) are internalized through specific receptors placed on neighboring cells (RAGEs); (vi) are cleared by autophagy; and (vii) are neurotoxic. These features are common for a-synuclein (in Parkinson's disease and other synucleinopathies), β-amyloid and tau (in degenerative dementia), SOD-1 and TDP43 (in amyotrophic lateral sclerosis), and PrPsc (in prion diseases). While in some diseases these features are common to both ENS and CNS, in others this remains a working hypothesis. Purpose This review analyzes GI alterations from a pathological perspective to assess whether the enteric nervous system (ENS) mirrors the neuropathology described in the CNS. We discuss the potential mechanisms that lead to the onset and spread of neurodegeneration within the gut, from the gut to the brain, and vice versa.

Original languageEnglish
Pages (from-to)1056-1065
Number of pages10
JournalNeurogastroenterology and Motility
Issue number12
Publication statusPublished - Dec 2011


  • Autonomic nervous system
  • Gastrointestinal tract
  • Neurodegenerative diseases
  • Prion disease
  • Synucleinopathies

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology


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