Scientists show the positive side of steroids

Scientists at Swansea University’s College of Medicine and the Karolinska Institute in Stockholm, Sweden have identified two steroids-type molecules that play an important role in the survival and production of nerve cells in the brain.

The discovery, which has been published online in the international journal Nature Chemical Biology, may be significant in the long term for the treatment of several diseases, such as Parkinson's disease.

The group at Karolinska’s Laboratory of Molecular Neurobiology have previously shown 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 neurons, plays an important role in a number of diseases, such as Parkinson's disease.  What was not known, however, was which molecules stimulate LXR in the brain, such that the production of new nerve cells could be initiated.

A collaboration between the Karolinska group and Professor William J Griffiths and Dr Yuqin Wang at Swansea University’s Institute of Mass Spectrometry, who are expert in the use of mass spectrometry to identify biomolecules, has led to the discovery of two steroid-type molecules that bind to LXR and activate it.

Prof William Griffiths“These two molecules are named cholic acid and 24S,25-epoxycholesterol, a bile acid and a close relative of cholesterol, respectively," said Professor William J Griffiths (pictured).

“The first molecule, 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.

“The other molecule, 24S,25-epoxycholesterol, influences the generation of new dopamine-producing nerve cells, which are important in controlling movement.”

One important conclusion of the study is that 24S,25-epoxycholesterol can be used to turn stem cells into midbrain dopamine-producing neurons, the cell type that dies in Parkinson’s disease.

Dr Yuqin WangDr Yuqin Wang (pictured) added: “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.”

The team’s research paper, “Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis”, is published online in leading journal Nature Chemical Biology.

The work at Swansea was supported by the UK Research Councils’ Biotechnology and Biological Sciences Research Council (BBSRC). Visit http://www.bbsrc.ac.uk/home/home.aspx.

For more information on Swansea University’s Institute of Mass Spectrometry visit http://www.swansea.ac.uk/medicine/instituteofmassspectrometry/, and on the Karolinska Institutet visit http://ki.se/?l=en.