Efrat Shavit Stein, Israel

Sheba Medical Center Neurology
Dr. Efrat Shavit-Stein is a scientific director at the neurology basic research lab at the Sheba Medical Center, Israel. She received here B.Sc. in life and medical sciences from Tel Aviv University, M.Sc. and Ph.D. in neuroscience from the Physiology and Pharmacology department in Tel Aviv University under the supervision of professor Joab chapman. She is a senior lecturer at Tel-Aviv University and actively participates in neuropharmacology teaching of medical students. Her major research interests are the involvement of coagulation proteins in neuroal function in health and disease and has made significant contribution in this fields. She published over thirty peer reviewed scientific papers and presented in many scientific meetings. She is collaborating with medical doctors from different disciplines to translate her research findings into novel therapies.

Presenter of 1 Presentation

FEAM: A NOVEL MODULATOR FOR NEUROINFLAMMATION

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
11:00 - 11:10
Session Icon
Pre Recorded

Abstract

Background and Aims

Neural inflammation is regulated by coagulation proteins including activated protein C (aPC) and its endothelial protein c receptor (EPCR) which together activate protease activated receptor 1 (PAR1) inducing anti-inflammatory effects. We have synthesized a novel molecule based on the binding site of FVII/aPC to EPCR (FEAM) and studied its effectiveness in the treatment of neuroinflammation.

Methods

An in- vitro model for neuroinflammation was induced by LPS applied to N9 microglia cells. In-vivo neuroinflammation was induced by LPS systemic injection to ICR mice and behavior was assessed by the stair-case test. Thrombin and aPC activity from cells and brains were measured by enzymatic fluorescence assays. Proliferation was measured by XTT activity assay. Coagulation factors and inflammation markers levels were evaluated by western blot and real-time PCR.

Results

FEAM prevented the LPS induced increased proliferation rate (1 vs 1.5 arbitrary units (aU), p<0.001) and PAR1 expression in N9 (1.7 vs. 1.2, p<0.001). FEAM also prevented the decreased aPC activity induced by LPS (0.46 vs 0.62 aU, p<0.003) and prevented the elevation of coagulation factors (FX and thrombin) and inflammatory markers (TNFα). In the whole animal model FEAM prevented the LPS induced elevated brain thrombin activity and other coagulation and inflammation factors. FEAM treatment induced improvement in general health indices such as weight, learning and memory and mobility.

Conclusions

In conclusion, FEAM modulation of the FVII-aPC-EPCR pathway may shift the thrombin/PAR1 pathway toward aPC-EPCR mediated protective downstream effects.

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