A Role for Neuronal Alpha-Synuclein in Gastrointestinal Immunity

Area of Science:

• Neuroscience
• Immunology
• Gastroenterology

Background:

• Alpha-synuclein (αS) is linked to Parkinson disease (PD) and accumulates in the enteric nervous system (ENS).
• The function of αS in the ENS and its role in gastrointestinal (GI) inflammation are unknown.
• Rodent studies suggest αS activates immune cells in the central nervous system.

Purpose of the Study:

• To investigate the role of αS in the innate immune defenses of the human GI tract.
• To determine if αS exhibits immune-modulatory activity in the ENS.

Main Methods:

• Immunostaining of endoscopic biopsies from pediatric patients with GI inflammation and norovirus-infected allograft recipients.
• Assessing αS-induced leukocyte migration and dendritic cell maturation in vitro.

Main Results:

• αS expression in the upper GI tract correlated with intestinal inflammation.
• Norovirus infection induced αS expression in intestinal allografts.
• Both monomeric and oligomeric αS attracted neutrophils and monocytes and stimulated dendritic cell maturation.

Conclusions:

• αS is expressed in the human ENS and directs intestinal inflammation.
• Common GI infections may play a role in Parkinson disease pathogenesis.