New insight into brain inflammation in neurological diseases

Neurological diseases, such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, multiple sclerosis, and stroke, involves brain inflammation. However, little is known about the mechanism of the inflammation. A new study, carried out by researchers including Leslie Freeman, Haitao Guo, Clément David, June Brickey, Sushmita Jha, and Jenny P.-Y. Ting at the University of North Carolina at Chapel Hill, has identified important molecules that trigger inflammation in the brain. Moreover, human patients with multiple sclerosis have large amounts of the same molecules in their brain. Thus, targeting these inflammatory molecules might be a way to treat multiple sclerosis. The study may also have profound implications in other neurological diseases.

In the study, Dr Jenny Ting and colleagues looked at lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination. They found that LPC triggers the inflammatory activation of mouse immune cells through two proteins called NLRP3 and NLRC4. Next, Ting's team used a mouse model of multiple sclerosis. In this model, mice received a chemical called cuprizone, leading to brain inflammation and demyelination. The researchers found that when mice did not have the two genes NLRC4 and NLRP3, the usual inflammatory activation of astrocytes and microglia was significantly decreased. The results suggest that NLRC4 and NLRP3 are involved in LPC-induced brain inflammation.

NLRC4 (NLR family CARD domain-containing protein 4) is best associated with causing the formation of the inflammasome, a multiproteinoligomerthat belongs to the innate immune system. NALP3 (NACHT, LRR and PYD domains-containing protein 3) is a component of the inflammasome that functions as a pathogen recognition receptor. The NLRC4 and NLRP3 proteins cause inflammation in response to certain microbes as well as non-microbial signals associated with tissue damage.

Study author Dr Haitao Guo noted that their study provides the first clear evidence that NLRC4 and NLRP3 play a key role in astrocytic and microglial inflammation, and LPC causes the inflammation. The study “NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes” was published 28 February 2017 in the Journal of Experimental Medicine. (NLRC4, NLRP3, and Recombinant FZD7 can be offered by CusAb.)