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Published on: August 28, 2021
Alpha-2-macroglobulin prevents platelet aggregation induced by brain-derived neurotrophic factor
Georges Jourdi1, Imane Boukhatem2, Pablo F Barcelona3
1Research Center, Montreal Heart Institute, Montreal, QC H1T 1C8, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada; Université Paris Cité, INSERM, Innovative Therapies in Haemostasis, F-75006 Paris, France; Service d'Hématologie Biologique, AP-HP, Hôpital Lariboisière, F-75010 Paris, France.
Alpha-2-macroglobulin (α2M) regulates brain-derived neurotrophic factor (BDNF) in blood. This protein complex inhibits BDNF-induced platelet activation, preventing constant platelet aggregation.
Area of Science:
- Hematology
- Neuroscience
- Biochemistry
Background:
- Brain-derived neurotrophic factor (BDNF) exhibits activating effects on isolated platelets.
- BDNF circulates in plasma, necessitating a mechanism to prevent continuous platelet activation.
Purpose of the Study:
- To investigate the mechanism regulating BDNF bioavailability and its effect on platelet activation in blood.
- To identify the role of alpha-2-macroglobulin (α2M) in modulating BDNF activity.
Main Methods:
- Molecular docking predicted protein-protein interactions between BDNF and α2M.
- Immunoprecipitation validated these interactions.
- Platelet aggregation assays (light transmission aggregometry) and phospho-blots assessed BDNF signaling and inhibition by α2M.
Main Results:
- Autologous plasma significantly inhibited BDNF-induced platelet aggregation.
- α2M formed stable complexes with BDNF, preventing its binding to the TrkB receptor.
- Both native and activated α2M inhibited BDNF-induced platelet aggregation in a concentration-dependent manner.
Conclusions:
- α2M acts as a physiological regulator of BDNF bioavailability in blood.
- α2M inhibits BDNF-induced platelet activation, serving as a crucial control mechanism.
- This study elucidates a novel pathway for controlling platelet responsiveness to BDNF.
