Characterization of the Expression and Pathogenicity of Alpha-Synuclein in the Enteric Nervous System

Misfolded alpha-Synuclein (α-Syn) is a main neuropathological hallmark of Parkinson’s Disease (PD). α-Syn is expressed not only in brain tissues, but also in the enteric nervous system (ENS). Here, we aimed to reevaluate the localization pattern of α-Syn in the ENS of PD patients and control subjects. Formalin-fixed and paraffin-embedded (FFPE) full-thickness colon resections were used to characterize α-Syn localization pattern in the ENS of control subjects. Additionally, α-Syn localization pattern was assessed by immunohistochemistry in FFPE deep rectal biopsies of PD patients using a conformation-specific α-Syn-antibody and compared to healthy controls. Seeding potential of α-Syn aggregates from rectal biopsies was further analyzed by α-Syn Seeding Aggregation Assays (α-syn-SAA). Characterization of the physiological localization pattern of α-Syn in the ENS confirms that α-Syn is widely detected in enteric neurons within myenteric and submucosal ganglia. While intraganglionic enteric glial cells (EGC) remained α-Syn-negative, α-Syn immunoreactivity was observed in mucosal EGC. This localization pattern remained unchanged in PD patients in comparison to controls. However, α-syn-SAAs confirmed the presence of misfolded α-Syn in FFPE biopsies of PD patients, but not in controls. These results confirm that α-Syn is not only expressed in enteric neurons, but also in mucosal EGC, indicating that this glial subpopulation may contribute to the regulation of α-Syn life-cycle. Unlike immunohistochemistry, α-syn-SAA may be used for the detection of pathological α-Syn in rectal biopsies of PD-patients with a high sensitivity. Development of such methodologies may help to better understand PD pathogenesis along the gut-brain axis in manifest and prodromal stages of PD.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Christian-Albrechts-Universität zu Kiel

Year

2026

Author dc:creator

• Kintrup, Carmen

Contributors dc:contributor

• Cossais, François
• Wulff, Peer Christian

• alpha-Synuclein
• Parkinson’s Disease
• enteric nervous system

Repository record source_url

https://macau.uni-kiel.de/receive/macau_mods_00008082

OAI identifier oai:identifier

oai:macau.uni-kiel.de:macau_mods_00008082