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.

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.