Activity‐dependent secretion of alpha‐synuclein by enteric neurons

Abstract

There is growing evidence supporting a role of extracellular alpha-synuclein in the spreading of Parkinson's disease (PD) pathology. Recent pathological studies have raised the possibility that the enteric nervous system (ENS) is one of the initial sites of alpha-synuclein pathology in PD. We therefore undertook this survey to determine whether alphasynuclein can be secreted by enteric neurons. Alphasynuclein secretion was assessed by immunoblot analysis of the culture medium from primary culture of ENS. We show that alpha-synuclein is physiologically secreted by enteric neurons via a conventional, endoplasmic reticulum/Golgidependent exocytosis, in a neuronal activity-regulated manner. Our study is the first to evidence that enteric neurons are capable of secreting alpha-synuclein, thereby providing new insights into the role of the ENS in the pathophysiology of PD.

Alpha-synuclein is associated with the synaptic vesicle apparatus in the human and rat enteric nervous system

“…The data suggest that growth and differentiation of postnatal enteric neurons promoted by GDNF involves a concomitantly increased gene expression of a-syn required for the functional integrity of enteric neuronal networks. This observation is in line with data described by Paillusson et al (2013) who reported that a-syn can be secreted by enteric neurons in an activity-dependent fashion.…”

Parkinson's disease as a member of Prion-like disorders

“…These primary cultures have been derived from rat, mouse, flies and even from human embryonic stem cells (Park and Lee, 2006;Rideout et al, 2004;Zhou et al, 2002Zhou et al, , 2000. Besides the species, also the region of the nervous systems from which the cell derive can vary from study to study, cerebellar granular cells (Monti et al, 2007), dorsal root ganglia , cortical and midbrain neurons (Rideout et al, 2003) and enteric neurons (Paillusson et al, 2013) just to name a few.…”

Comparison study of gut microbiota in case of Parkinson’s disease and other neurological disorders

“…Кроме того, в микробиоте кишечника пациентов с болезнью Паркинсона отмечается повышение представленности бактерий, способ-ных оказывать влияние на работу нейронов. Так Lactobacillus mucosae, содержание которой в ми-кробиоте кишечника повышается как в сравнении с другими неврологическими заболеваниями, так и при сравнении с группой здорового контроля на финской популяции [7], способна влиять на секрецию α-синуклеина через взаимодействия с нейронами кишечника [33,34]. Кроме того, одно из производных β-индолилуксусной кислоты, вы-деляемой ранее упоминавшийся Intestinibacter bartlettii, -5-гидроксииндолилуксусная кислота -является метаболитом серотонина и способно оказывать влияние на работу нервной системы, в частности понижать болевой порог [35].…”