A genetic defect tied to a variety of neurodegenerative diseases and mental illnesses changes how cells starved of sugar metabolize fatty compounds known as lipids, a new study led by researchers from the Johns Hopkins Bloomberg School of Public Health shows. The finding could lead to new targets to treat these diseases, which currently have no cure or fully effective treatments.
Taken together, these results suggest that the genetic defect, mutations in a gene called C9orf72, lead to greater amounts of a protein that causes cells to overproduce lipids and an enzyme called NOX2. The enzyme NOX2, which is known to cause oxidative stress that can damage cells, has also been shown to be elevated in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
The findings were published online Oct. 26 in the journal Genes & Development.
“Cells with this mutation act as if they’re chronically under stress, which could underlie the pathology of diseases associated with this defect,” says Dr. Jiou Wang, an associate professor in the Bloomberg School’s department of biochemistry and molecular biology. “Our study raises the question of whether we should be looking at problems with lipid metabolism as a potential cause for these diseases.”