The discovery, published in the journal Nature Chemical Biology, could help in the development of new treatments for neurological diseases such as Parkinson’s disease.
The two steroid-like molecules influence neurons in the brain. Image: Thinkstock 2013
Co-investigator professor William Griffiths, chair in mass spectrometry at Swansea University, said: “We believe that the identification of these molecules represents an important step toward understanding the role of lipids in brain development and toward the development of new therapies for neurological disorders such as Parkinson’s disease.”
Previous work from the Karolinska group showed that receptors known as ‘liver X receptors’, or LXR, are necessary for the production of different types of nerve cells, or neurons, in the developing brain. One of these types, the midbrain dopamine-producing neuron, plays an important role in a number of diseases including Parkinson’s disease.
However it was not known which molecules stimulate these receptors, so that the production of new neurons could be initiated.
The collaboration between the BBSRC-funded scientists in Swansea and the Karolinska group identified two steroid-type molecules that bind to and activate LXR receptors in mice and zebrafish.
One of these molecules, 24S,25-epoxycholesterol, can be used to turn stem cells into midbrain dopamine-producing neurons, the cell type that dies in Parkinson’s disease.
The other molecule identified, cholic acid, influences the production and survival of neurons in what is known as the ‘red nucleus’, which is important for incoming signals from other parts of the brain.
Prof Griffiths said: “This finding opens the possibility of using steroid-type molecules in future regenerative medicine, since new dopamine-producing cells created in the laboratory could be used for transplantation to patients with Parkinson’s disease.
“This is an exciting area for further research.”
Notes to editors
Reference: ‘Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis‘ is available at: www.nature.com/nchembio/journal/vaop/ncurrent/abs/nchembio.1156.html
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