Scientists see the link between oxidative stress and neurological disorders

Indian scientists have discovered a new function of a gene already known to play a role in neurological disorders.

Scientists at the Indian Institute of Scientific Education and Research (IISER) in Pune have discovered that the gene, ABHD12, is involved in attenuating oxidative stress-induced cell death in brain cells by destroying the brain. Oxidized state of a lipid, phosphatidylserine, found in the cell membrane.

Given the known function of this gene in neurological disorders, the new discovery indicates plausible links between oxidative stress and neurological disorders, according to results published in the journal Nature Chemical Biology.

A cell has a finite life and is driven by the overproduction of reactive oxygen species (ROS) resulting in oxidative stress. ROS is a byproduct of the functioning of mitochondria – a powerhouse of the cell. ROS damage lipid membranes or the cell boundary, DNA as well as cell proteins.

Previous studies have shown that phosphatidylserine, a clbad of lipids present in the cell membrane, when oxidized by ROS, reverses their direction from the inside of the cell to the outside; which triggers cell death.

The IISER study revealed that ABHD12, a gene encoding serine hydrolase lipase, can degrade the oxidized form of lipid phosphatidylserine, thereby preventing cell death.

"The mutation in ABHD12 causes a human neurological disorder called PHARC (acronym for polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataract). Our findings will allow a study of PHARC, a progression of the pathology and possibly develop new therapeutic interventions for the treatment of this early-onset disease, "said Dr. Siddhesh Kamat, head of the team's team. research, during an interview with India Science Wire.

For this study, scientists first synthesized a chemical fraction that could release ROS into cultured mammalian cells, thus mimicking the environment of oxidative stress in the cell. After administering this ROS stress, the scientists measured levels of oxidized PS. To obtain a lipase enzyme that metabolizes oxidized PS, scientists used various lipase inhibitors and discovered that three inhibitors whose application increased the oxidized PS in the cell. Proteome badysis helped the researchers conclude that a lipase encoded by the ABHD12 gene attenuates cell death by breaking down oxidized PS.

The research team led by Dr. Siddhesh Kamat included Dhanashree S. Kelkar, Neelay Mehendale, Shubham Singh and Alaumy Joshi, Amol Mhetre, Abinaya Rajendran, Govindan Ravikumar, Ajay Kumar Sharma and Harinath Chakrapani.