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conferenceseries
.com
Volume 7, Issue 6 (Suppl)
J Alzheimers Dis Parkinsonism, an open access journal
ISSN: 2161-0460
Dementia 2017
October 16-18, 2017
ALZHEIMER’S DISEASE & DEMENTIA
October 16-18, 2017 | Rome, Italy
9
th
International Conference on
Sphingosine-1-phosphate receptor 1 (S1PR-1): A new target for the treatment of Tau-related
pathologies
Guy Massicotte, Frédéric St-Cyr Giguère
and
Michel Cyr
University of Quebec, Canada
T
au proteins are known to helpmaintaining the structure of a neuron, including tiny tube-like structures calledmicrotubules,
which deliver nutrients throughout cells. However, when hyperphosphorylated, these proteins can become toxic for
neurons by forming tangles in the hippocampus; one important region of the brain early affected by Alzheimer’s disease.
Researchers believe that therapies capable to limit Tau phosphorylation in the hippocampus may reduce tangle formation
and ultimately intervene in the development of Alzheimer’s disease and other Tau-related disorders. Global sphingosine-1-
phosphate receptor (S1PR) agonists were recently found to exert neuroprotective effects in several model systems reproducing
different brain disorders. Consequently, we assessed the influence of such compounds on Tau phosphorylation in the
hippocampus. Transverse rat hippocampal slices were prepared with a McIlwain tissue chopper and placed on a nylon mesh
in a liquid-gas interface chamber. They were treated for a period of 3 hours with S1PR-1 (SEW2871) and S1PR-3 (CYM5541)
agonists. Tau phosphorylation was then estimated by Western blotting procedures. We noticed an important reduction in
Tau-Ser262 phosphorylation after hippocampal slice treatments with the S1PR-1 agonist SEW2871. In terms of molecular
mechanisms, SEW2871-induced Tau-Ser262 dephosphorylation seems to be dependent on AMPK (AMP-activated protein
kinase) inactivation, a process involving the protein phosphatase PP2A. Comparable experiments indicate that neither Tau
nor AMPK were influenced by the S1PR-3 agonist CYM5541. Our results suggest a new target for Tau dephosphorylation
and provide an insight into the potential therapeutic effects of S1PR agonists in Alzheimer’s disease and other Tau-related
pathologies.
Biography
Guy Massicotte’s work is mainly focusing on the role phospholipase enzymes and lipids in glutamate receptor regulation during both normal and neuropathological
conditions. Full professor in human physiology at the University of Québec, He is actually investigating the role of ceramide derivatives in premature ageing of the
brain. He is the author of 80 publications, some being published in top-quality journals such as Nature, Proceedings of the National Academy of Sciences, FASEB
Journal, Diabetes, Neuroscience and Biobehavioral Reviews.
guy.massicotte@uqtr.caGuy Massicotte et al., J Alzheimers Dis Parkinsonism 2017, 7:6(Suppl)
DOI: 10.4172/2161-0460-C1-034