Scientists Discover How Neuroactive Steroids Dampen Inflammatory Signaling in Immune System and Brain

Led by Leslie Morrow, PhD, research shows how new compounds could target specific brain cell receptors to treat a wide variety of conditions, such as alcoholism, Alzheimer’s, depression, and posttraumatic stress.

Scientists Discover How Neuroactive Steroids Dampen Inflammatory Signaling in Immune System and Brain click to enlarge Schematic of activated TLR4 signal inhibited by neurosteroids.

February 13, 2019

Leslie Morrow, PhDCHAPEL HILL, NC – For the first time, scientists discovered how neuroactive steroids naturally found in the brain and bloodstream inhibit the activity of a specific kind of protein called Toll-like receptors (TLR4), which have been known to play a role in inflammation in many organs, including the brain.

This UNC School of Medicine-University of Maryland collaboration, published in Nature Scientific Reports, shows how the neurosteroid allopregnanolone prevents the activation of pro-inflammatory proteins important for gene regulation, as well as the creation of cytokines, which are known to be involved in many different inflammatory conditions. Inflammatory cell signaling in the brain is heightened in many neuropsychiatric conditions, including alcohol use disorder, depression, and posttraumatic stress. It is also seen in sepsis, epilepsy, multiple sclerosis, and Alzheimer’s disease.

“It has been very difficult to treat brain disease that involves inflammation, but allopregnanolone’s inhibition of TLR4 signaling activation in macrophages and the brain provides hope that we can develop better therapies to help millions of people suffering with these conditions,” said senior author A. Leslie Morrow, PhD, the John Andrews Distinguished Professor in the Departments of Psychiatry and Pharmacology at the UNC School of Medicine.

~excerpt from the full article by Mark Derewicz on SOM News...

read the journal article in Nature Scientific Reports published Feb. 4, 2019...