EVBO Publication Highlight July 2020

Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature.

Bilal N Sheikh, Sukanya Guhathakurta, Tsz Hong Tsang, Marius Schwabenland, Gina Renschler, Benjamin Herquel, Vivek Bhardwaj, Herbert Holz, Thomas Stehle, Olga Bondareva , Nadim Aizarani, Omar Mossad, Oliver Kretz, Wilfried Reichardt, Aindrila Chatterjee, Laura J Braun, Julien Thevenon, Herve Sartelet, Thomas Blank, Dominic Grün, Dominik von Elverfeldt, Tobias B Huber, Dietmar Vestweber, Sergiy Avilov, Marco Prinz, Joerg M Buescher, Asifa Akhtar.

Nat Cell Biol. 2020 Jul;22(7):828-841. DOI: 10.1038/s41556-020-0526-8. Epub 2020 Jun 15.

Pub High Jul 20

Key findings

1. The chromatin MOF-NSL complex maintains transcription of neural metabolic networks in the developing brain.

2. Neural-specific depletion of MOF-NSL complex members results in an aberrant metabolic profile.

3. Abnormal accumulation of free fatty acids in neural cells can be directly detected by neighboring vascular pericytes.

4. Free fatty acids trigger a TLR4-NFkB driven inflammatory response in vascular pericytes leading to breakdown of neural vasculature.

5. Metabolites can mediate inter-cellular communication in the brain.