While the detailed mechanisms by which activation of SREBP-1 leads to brain cell death remain to be established, the researchers discovered a way to inhibit SREBP-1 and thereby significantly reduce cell death.
"We developed a drug that can stabilize Insig-1, which in turn inhibits the activity of SREBP-1," says Dr. Max Cynader, co-lead on the study, a Canada Research Chair in Brain Development, and the Director of the Brain Research Centre. "By doing so, we were able to prevent cell death."
The researchers also found that the drug works post-stroke in animal models. "When we administered it post-stroke, there was less brain cell damage 30 days later than compared to controls," says Dr. Wang. "This is important because previous studies focused on blocking the NMDA receptors in order to prevent cell death, but this approach didn't work because it affected normal cell function and had a relatively short therapeutic window. The drug we studied works downstream of NMDA receptors and appears to have less detrimental side effects with a much improved therapeutic window."
Further investigations will help researchers understand how SREBP-1 causes cell death and to further determine efficacy of the drug. As well, because of the protein's connection to cholesterol synthesis and other cellular functions, further investigations may reveal if it has a role in other neurological disorders, such as ALS, and whether the drug might be effective for those conditions as well.
|Contact: Melissa Ashman|
University of British Columbia