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4 t h E u r o S c i C o n C o n f e r e n c e o n
Neurology & Neurological
Disorders
Neurology 2018
J u l y 1 2 - 1 3 , 2 0 1 8
P a r i s , F r a n c e
Page 94
Journal of Neurology and Neuroscience
ISSN: 2171-6625
Objective: To determine whether microbiome derived short chain fatty acid (SCFA) may modulate abnormal α-¬synuclein
misfolding and seeding activity of α-synuclein to support the hypothesis of potential novel therapeutic approaches.
Background: There is growing evidence from both in vivo and in vitro studies that in many neurodegenerative disorders, including
synucleinopathies, cell-to-cell transmission of a pathological, misfolded protein occurs and may be a vehicle for spreading of
pathology throughout the brain. We hereby investigate whether microbiota-derived SCFAs may help attenuate the misfolding of
α-synuclein and their effects on seeding synucleinopathy.
Design/Methods: In vitro aggregation of α-synuclein in the absence or in the presence of SCFAs at a molar ratio of 1:1 or 1:4
α¬-synuclein:SCFA, were monitored by using independent assays: photo-induced cross-linking of unmodified proteins assay,
thioflavin-T, fluorescence assay, or electron microscopy.
Results: We found that select microbiome-derived SCFAs significantly interfere with α-synuclein aggregation in independent in
vitro assays.
Conclusions: Selected microbiome-derived SCFAs may help protect against diverse synucleinopathies by converting dietary
fibers into biologically available SCFAs which significantly interfere with aggregation of disease-specific α-¬synuclein into toxic
aggregates. Ongoing cell-based systems, which detect levels of α-synuclein by florescent FRET signalling, will clarify the impact
of this anti-aggregation activity of SCFAs on interference of α-synuclein seeding activity that is critical for the propagation of
α-synuclein mediated pathologies. This data will help to clarify distinct α-synuclein seeding activity from α-synuclein isolated
from post-mortem brain samples of patients with Parkinson’s disease, multiple systemic atrophies, and other synucleinopathies,
leading to novel therapeutic approaches
Role of microbiota derived short chain fatty acids
in α-Synuclein aggregation and seeding
Giulio Pasinetti, Risham Singh and Lap Ho
Icahn School of Medicine, Mount Sinai, USA
J Neurol Neurosci 2018, Volume: 9
DOI: 10.21767/2171-6625-C1-009