Reach Us +44-7447-215064
All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.

Role of microbiota derived short chain fatty acids in α-Synuclein aggregation and seeding

4th EuroSciCon Conference on Neurology & Neurological Disorders
July 12 -13, 2018 Paris , France

Giulio Pasinetti, Risham Singh and Lap Ho

Icahn School of Medicine, Mount Sinai, USA

Posters & Accepted Abstracts: J Neurol Neurosci

DOI: 10.21767/2171-6625-C1-009

Abstract

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

Flyer image

Abstracted/Indexed in

  • Google Scholar
  • Open J Gate
  • Genamics JournalSeek
  • The Global Impact Factor (GIF)
  • China National Knowledge Infrastructure (CNKI)
  • Directory of Research Journal Indexing (DRJI)
  • WorldCat
  • Proquest Summons
  • Scientific Journal Impact Factor
  • Secret Search Engine Labs