Characterization of α-synuclein (α-syn) in normal human jejunum and its correlations with the neuroendocrine system

Alpha-synuclein (α-syn) is a presynaptic neuronal protein and its structural alterations play an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD) (1). It has been originally described in the brain and aggregated α-syn has also been found in the peripheral nerves including the enteric nervous system (ENS) of PD patients (2). ENS is a network of neurons and glia found in the gut wall which controls gastrointesti-nal function independently from the central nervous system. Moreover, two types of epithelial cells are crucial in the creation of an interface between the lumen and the ENS: they are the tuft cells and the enterochromaffin cells (EECs) (3-4). In addition, the abundant enteric glial cells (EGCs) in the intesti-nal mucosa play a key role in controlling the intestinal epithelial barrier (5). Our aim has been to localize and characterize the presence of α-syn in the normal human jejunum wall. Surgical specimens of proximal jejunum wall were collect-ed from patients submitted to pancreaticoduodenectomy and intestinal sec-tions underwent immunohistochemical procedure using monoclonal antibody for α-syn. α-Syn has been found both at the level of ENS and the epithelial cells. To characterize α-syn immunoreactive epithelial cells we used markers as choline acetyltransferase (ChAT), useful to the identification of tuft cells (3). Then, we evaluated the co-presence of α-syn with 5-hydroxytryptamine (5-HT), expressed in EECs (4). Finally, we used the low-affinity nerve growth factor re-ceptor (p75NTR), to detect peripheral EGCs. The presence of α-syn has been demonstrated in EECs but not in the tuft cells. Additionally, p75NTR has been highlighted in EGCs of the mucosal layer, and co-localized with α-syn in EECs but not in ChAT-positive cells. These findings suggest that α-syn could play a crucial role in synaptic transmission of the ENS and may contribute to maintain the integrity of the epithelial barrier of the small intestine through EECs.