Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis.

26 February 2021

ESNI Journal Club March 30, 2021 at 3:00pm CET

ESNI will host Dr. Gesine Saher and Dr. Stefano Berghoff (Max Plank Institute of Experimental Medicine, Germany) to answer question about there article Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis.

“The repair of inflamed, demyelinated lesions as in multiple sclerosis (MS) necessitates the clearance of cholesterol-rich myelin debris by microglia/macrophages and the switch from a pro-inflammatory to an anti-inflammatory lesion environment. Subsequently, oligodendrocytes increase cholesterol levels as a prerequisite for synthesizing new myelin membranes. We hypothesized that lesion resolution is regulated by the fate of cholesterol from damaged myelin and oligodendroglial sterol synthesis. By integrating gene expression profiling, genetics and comprehensive phenotyping, we found that, paradoxically, sterol synthesis in myelin-phagocytosing microglia/macrophages determines the repair of acutely demyelinated lesions. Rather than producing cholesterol, microglia/macrophages synthesized desmosterol, the immediate cholesterol precursor. Desmosterol activated liver X receptor (LXR) signaling to resolve inflammation, creating a permissive environment for oligodendrocyte differentiation. Moreover, LXR target gene products facilitated the efflux of lipid and cholesterol from lipid-laden microglia/macrophages to support remyelination by oligodendrocytes. Consequently, pharmacological stimulation of sterol synthesis boosted the repair of demyelinated lesions, suggesting novel therapeutic strategies for myelin repair in MS.”

You may be interested

Senza categoria

Tuesday August 30

stine - 23 May 2022

DATE & TIME: Tuesday August 30 - 3:00pm - 4:00pm CEST ARTICLE: Identification of four novel T cell autoantigens and personal autoreactive profiles…

Senza categoria

Tuesday June 28

stine - 27 April 2022

DATE & TIME: Tuesday June 28 - 3:00pm - 4:00pm CEST  ARTICLE: Twin study reveals non-heritable immune perturbations in multiple sclerosis Pub…

Senza categoria

Tuesday May 31

stine - 21 March 2022

DATE & TIME: Tuesday May 31 - 3:00pm - 4:00pm CEST ARTICLE: The lung microbiome regulates brain autoimmunityPub med: pubmed.ncbi.nlm.nih.gov/35197636MODERATOR: Maja Jagodic (Karolinska…