New findings on 'key players' in brain inflammation
News Mar 07, 2015
Inflammatory processes occur in the brain in conjunction with stroke and neurological diseases such as Alzheimer's and Parkinson's disease. Researchers from Lund University and Karolinska Institutet in Sweden, in close cooperation with a group led by Professor José L. Venero at the University of Seville, have presented new findings about some of the 'key players' in inflammation. In the long term, these findings could lead to new treatments.
One of these key players is a receptor called TLR4. The receptor plays such an important role in the body's innate immune system that the researchers who discovered it were awarded the 2011 Nobel Prize in Physiology or Medicine. The other key player is a protein called galectin-3, which is absent in healthy brains but present in a brain suffering ongoing inflammation.
"We have demonstrated that galectin-3 is secreted by microglial cells, a type of immune cell in the brain. The protein binds to the TLR4 receptor and amplifies the reactions that lead to inflammation. More galectin-3 is produced and binds to the immune cells, and the immune response is further intensified in a self-sustaining process," explained Tomas Deierborg, associate professor at Lund University.
The researchers have demonstrated the importance of the link between the two 'key players' using various different methods and in laboratory tests, animal experiments and human trials. They have shown that mice genetically modified to be incapable of synthesising galectin-3 show a lower inflammatory response and less brain damage after a heart attack. Mice with a model of Parkinson's disease also suffer less brain damage if they do not have the gene for galectin-3.
The researchers have also observed the interaction between galectin-3 and TLR4 in the brains of people who died of a stroke.
"We believe that this link could be part of the explanation for the residual disability that stroke patients often experience. High levels of galectin-3 remain in the brains of these patients long after the stroke, which may explain why the inflammatory response continues to cause damage and does not subside," said Miguel Angel Burguillos, currently working at Queen Mary University of London.
Galectin-3 is already a target for pharmaceutical companies trying to develop agents that hinder the harmful effects of the protein in neuroinflammatory diseases. The new findings on the effects and role of the protein in a diseased or damaged brain should provide important input to this work.
"Previously, it was acknowledged that galectin-3 contributed to the inflammatory response but the mechanism wasn't clear. The protein is not present in a healthy brain, only in one that is suffering an inflammatory response. Now that we understand the mechanism, this will make it easier to develop more effective treatments," said Dr Deierborg.
Note: Material may have been edited for length and content. For further information, please contact the cited source.
Miguel Angel Burguillos, Martina Svensson, Tim Schulte, Antonio Boza-Serrano, Albert Garcia-Quintanilla, Edel Kavanagh, Martiniano Santiago, Nikenza Viceconte, Maria Jose Oliva-Martin, Ahmed Mohamed Osman, Emma Salomonsson, Lahouari Amar, Annette Persson, Klas Blomgren, Adnane Achour, Elisabet Englund, Hakon Leffler, Jose Luis Venero, Bertrand Joseph, Tomas Deierborg. Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation. Cell Reports, Published Online March 5 2015. doi: 10.1016/j.celrep.2015.02.012
Researchers Find a Way to Separate Side Effects of Opioid Drugs Reducing RiskNews
Scientists have discovered a way to separate these two effects -- pain relief and breathing, opening a window of opportunity to make effective pain medications without the risk of respiratory failure.READ MORE
Biological Mechanism of a Leading Cause of Childhood Blindness RevealedNews
Scientists have revealed the pathology of cells and structures stricken by optic nerve hypoplasia, a leading cause of childhood blindness in developed nations.READ MORE
Machine Learning: Helping Determine How a Drug Affects the BrainNews
Machine learning could improve our ability to determine whether a new drug works in the brain, potentially enabling researchers to detect drug effects that would be missed entirely by conventional statistical tests, finds a new UCL study published today in Brain.READ MORE