title: Parallel manifestations of neuropathologies in the enteric and central nervous systems.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Natale
authors.forename: L
authors.initials: L
authors.lastname: Pasquali
authors.forename: A
authors.initials: A
authors.lastname: Paparelli
authors.forename: F
authors.initials: F
authors.lastname: Fornai
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology; D017615:Enteric Nervous System / Q000473:pathology* / Q000503:physiopathology; D041981:Gastrointestinal Tract / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology* / Q000503:physiopathology; D017096:Prion Diseases / Q000473:pathology / Q000503:physiopathology; D011328:Prions / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D011328:Prions; D051844:alpha-Synuclein