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Inflammatory bowel disease induces pathological α-synuclein aggregation in the human gut and brain

Espinosa-Oliva, Ana M. (author)
University Hospital Virgen del Rocío,University of Seville
Ruiz, Rocío (author)
University of Seville,University Hospital Virgen del Rocío
Soto, Manuel Sarmiento (author)
University of Oxford,University of Seville,University Hospital Virgen del Rocío
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Boza-Serrano, Antonio (author)
Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups,University of Seville,University Hospital Virgen del Rocío
Rodriguez-Perez, Ana I. (author)
CIBER Enfermedades Neurodegenerativas (CIBERNED),CIBER de Fisiopatología Obesidad y Nutricion (CIBEROBN)
Roca-Ceballos, María A. (author)
University Hospital Virgen del Rocío,University of Seville
García-Revilla, Juan (author)
University of Seville,University Hospital Virgen del Rocío
Santiago, Marti (author)
University of Seville,University Hospital Virgen del Rocío
Serres, Sébastien (author)
University of Oxford,University of Nottingham
Economopoulus, Vasiliki (author)
University of Oxford
Carvajal, Ana E. (author)
University of Seville
Vázquez-Carretero, María D. (author)
University of Seville
García-Miranda, Pablo (author)
University of Seville
Klementieva, Oxana (author)
Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Medicinsk mikrospektroskopi,Forskargrupper vid Lunds universitet,LINXS - Institute of advanced Neutron and X-ray Science,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,LU profilområde: Proaktivt åldrande,Other operations, LTH,Faculty of Engineering, LTH,Medical Microspectroscopy,Lund University Research Groups,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas,LU Profile Area: Proactive Ageing
Oliva-Martín, María J. (author)
University of Seville,University Hospital Virgen del Rocío
Deierborg, Tomas (author)
Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Neuroinflammation,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Department of Experimental Medical Science,Faculty of Medicine,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas
Rivas, Eloy (author)
University Hospital Virgen del Rocío
Sibson, Nicola R. (author)
University of Oxford
Labandeira-García, José L. (author)
CIBER de Fisiopatología Obesidad y Nutricion (CIBEROBN),CIBER Enfermedades Neurodegenerativas (CIBERNED)
Machado, Alberto (author)
University Hospital Virgen del Rocío,University of Seville
Peral, María J. (author)
University of Seville
Herrera, Antonio J. (author)
University Hospital Virgen del Rocío,University of Seville
Venero, José L. (author)
University Hospital Virgen del Rocío,University of Seville
de Pablos, Rocío M. (author)
University Hospital Virgen del Rocío,University of Seville
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 (creator_code:org_t)
2024
2024
English.
In: Neuropathology and Applied Neurobiology. - 0305-1846. ; 50:1
Related links:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Aims: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. Methods: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. Results: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. Conclusion: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

alpha-synuclein
inflammatory bowel disease
neurodegeneration
neuroinflammation
Parkinson's disease

Publication and Content Type

art (subject category)
ref (subject category)

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