RT Journal Article
SR Electronic
T1 LPS INDUCES AGGREGATION OF α-SYNUCLEIN IN MONOCYTES
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP e4
OP e4
DO 10.1136/jnnp-2015-312379.93
VO 86
IS 11
A1 Herjan Koopman
A1 Simon Jackson
A1 Oleg Anichtchik
A1 Camille Carroll
YR 2015
UL http://jnnp.bmj.com/content/86/11/e4.188.abstract
AB It is well recognised that Parkinson's disease (PD) is associated with gastrointestinal problems appearing before onset of motor symptoms. An important role for the enteric nervous system (ENS) has been suggested. We hypothesize that inflammatory responses are involved in the onset and progression of PD, with a pivotal role for monocytes/macrophages in the gut. We show that lipopolysaccharide (LPS) can induce the expression and aggregation of monomeric α-synuclein in a human monocyte cell line (MM6). 24 Hours stimulation with LPS resulted in 3-6.5-fold increase in monomeric α-synuclein (determined by Western blotting), whilst tetrameric α-synuclein increased 1.3-2.2-fold. Preliminary results suggest that trimeric α-synuclein is secreted extracellularly after stimulation with LPS. Specificity of the observed bands was confirmed by pre-absorbing the antibody with recombinant α-synuclein. These findings were supported by immunocytochemistry: double immunofluorescence showed co-localization of aggregated α-synuclein with an antibody recognizing only oligomeric α-synuclein, confirming the presence of aggregates. These results suggest a role for inflammatory responses leading to increased monomeric and aggregated α-synuclein levels in monocytes. Secreted α-synuclein oligomers could mimic ‘prion-like’ spreading of aggregates to neurons, as observed in interneuronal transfer. The combination of aggregated α-synuclein with inflammatory mediators could influence the ENS, affecting onset and progression of PD.