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Tau accumulates in Crohn's disease gut

Research output: Contribution to journalArticle

Alice Prigent, Guillaume Chapelet, Adrien de Guilhem de Lataillade, Thibauld Oullier, Emilie Durieu, Arnaud Bourreille, Emilie Duchalais, Kevin Hardonniere, Michael Neunlist, Wendy Noble, Saadia Kerdine-Romer, Pascal Derkinderen, Malvyne Rolli-Derkinderen

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Abstract

A sizeable body of evidence has recently emerged to suggest that gastrointestinal inflammation might be involved in the development of Parkinson’s disease. There is now strong epidemiological and genetical evidence linking Parkinson's disease to inflammatory bowel diseases and we recently demonstrated that the neuronal protein alpha-synuclein, which is critically involved in Parkinson’s disease pathophysiology, is upregulated in inflamed
segments of Crohn’s colon. The microtubule associated protein tau is another neuronal protein critically involved in neurodegenerative disorders but, in contrast to alpha-synuclein, no data are available about its expression and phosphorylation patterns in inflammatory bowel diseases. Here, we examined the expression levels of tau isoforms, their phosphorylation profile and truncation in colon biopsy specimens from 16 Crohn’s disease and 6 ulcerative colitis patients and compared them to samples from 16 controls. Additional experiments were performed in full thickness segments of colon of 5 Crohn’s disease and 5 control subjects, in primary cultures of rat enteric neurons and in Nrf2 knockout mice. Our results show the upregulation of two main human tau isoforms in the enteric nervous system in Crohn’s disease but not in ulcerative colitis. This upregulation was not
transcriptionally regulated but instead likely resulted from a decrease in protein clearance via an Nrf2 pathway. Our findings, which provide the first detailed characterization of tau in Crohn’s disease, suggest that the key proteins involved in neurodegenerative disorders such as alpha-synuclein and tau, might also play a role in Crohn’s disease.

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