English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

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

Sheikh, B. N., Guhathakurta, S., Tsang, T. H., Schwabenland, M., Renschler, G. V., Herquel, B., et al. (2020). Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature. Nature Cell Biology, 22, 828-841. doi:org/10.1038/s41556-020-0526-8.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
Sheikh et al. 2020.pdf (Publisher version), 18MB
 
File Permalink:
-
Name:
Sheikh et al. 2020.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute of Immunobiology and Epigenetics, MFIB; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Sheikh, Bilal N.1, Author
Guhathakurta, Sukanya1, Author              
Tsang, Tsz Hong1, Author
Schwabenland, Marius2, Author
Renschler, Gina Vanessa1, Author              
Herquel, Benjamin1, Author              
Bhardwaj, Vivek1, Author
Holz, Herbert1, Author              
Stehle, Thomas1, Author              
Bondareva, Olga2, Author
Aizarni, Nadim1, Author
Mossad, Omar2, Author
Kretz, Oliver2, Author
Reichardt, Wilfried2, Author
Chatterjee, Aindrila1, Author
Braun, Laura J.2, Author
Thevenon, Julien2, Author
Sartelet, Herve2, Author
Blank, Thomas2, Author
Grün, Dominic1, Author              
von Elverfeldt, Dominik2, AuthorHuber, Tobias B.2, AuthorVestweber, Dietmar2, AuthorAvilov, Sergiy1, Author              Prinz, Marco2, AuthorBüscher, Jörg Martin1, Author              Akhtar, Asifa1, Author               more..
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243640              
2External Organizations, ou_persistent22              

Content

show
hide
Free keywords: -
 Abstract: Mutations in chromatin-modifying complexes and metabolic enzymes commonly underlie complex human developmental syn-dromes affecting multiple organs. A major challenge is to determine how disease-causing genetic lesions cause deregulation of homeostasis in unique cell types. Here we show that neural-specific depletion of three members of the non-specific lethal (NSL) chromatin complex—Mof, Kansl2 or Kansl3—unexpectedly leads to severe vascular defects and brain haemorrhaging. Deregulation of the epigenetic landscape induced by the loss of the NSL complex in neural cells causes widespread metabolic defects, including an accumulation of free long-chain fatty acids (LCFAs). Free LCFAs induce a Toll-like receptor 4 (TLR4)–NFκB-dependent pro-inflammatory signalling cascade in neighbouring vascular pericytes that is rescued by TLR4 inhibition. Pericytes display functional changes in response to LCFA-induced activation that result in vascular breakdown. Our work estab-lishes that neurovascular function is determined by the neural metabolic environment.

Details

show
hide
Language(s): eng - English
 Dates: 2020-06-15
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: org/10.1038/s41556-020-0526-8
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Nature Cell Biology
  Other : 'Nat. Cell Biol.'
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : Springer Nature
Pages: - Volume / Issue: 22 Sequence Number: - Start / End Page: 828 - 841 Identifier: ISSN: 1465-7392
CoNE: https://pure.mpg.de/cone/journals/resource/954925625310