by Mir Rameez Raja
SRINAGAR: A researcher from Jammu and Kashmir has played a lead role in identifying a previously undescribed cellular process that may explain how the brain ages and grows vulnerable to neurodegenerative disease.
Dr Nawab John Dar, a postdoctoral researcher at the Salk Institute for Biological Studies in La Jolla, California, is the co-corresponding author on a new study that introduces the term “chronoferroptosis”, a chronic stress pathway in which neurons do not die outright but gradually lose their resilience, becoming increasingly susceptible to the kind of damage seen in Alzheimer’s and Parkinson’s disease. The study was published in the peer-reviewed journal Cell Death Discovery on June 18, 2026.
Scientists have long observed that iron accumulates inside neurons as people age. Early in life, this build-up appears to have little effect, but later in life, it can contribute to a slow decline of the cells. The Salk team, led by Dr Dar alongside senior author Dr Pamela Maher, a Research Professor at the institute founded by polio vaccine pioneer Jonas Salk, set out to understand exactly how this slow accumulation feeds into disease.
Dr Dar was careful to stress that iron itself is not the problem. It is an essential mineral, found in foods such as leafy greens, cereals, lean meats and seafood, helping red blood cells carry oxygen and supporting other vital functions. As he put it, “It isn’t the iron itself that is a problem with age. It is this accumulation of iron over time that is the problem.”
The real puzzle, according to the researchers, was the delay between cause and effect. The team suspects iron builds up because the cell’s iron export machinery begins to fail, so iron enters as usual but is not properly removed, yet for a long time, this does not appear to harm the neuron. Dr Dar said most prior research had not been designed to capture this. “People have been doing these experiments, looking at iron exposure’s influence on cells over short 24-to-48-hour spans. But if neurodegenerative disorders are progressive, shouldn’t we have a cellular model that is progressive, too?”
To address this gap, the team built what is described as the first progressive model of iron accumulation in neuronal cells, using a human-derived nerve cell line, and compared brief, acute exposure of 6 to 8 hours against chronic exposure over 9 days, using identical doses.
Dr Maher, who has studied ferroptosis, an iron-dependent form of cell death driven by a process called lipid peroxidation, for decades, offered a homely analogy for the underlying chemistry: “It is like the cellular equivalent of when a cooking oil or nut goes bad. The fats in that oil or nut have undergone peroxidation.”
What surprised the researchers was that, over the longer timeframe, the process did not necessarily kill the cells outright. Instead, ferroptosis appeared to act as a cellular stress pathway: briefly exposed neurons showed very little biochemical change, while chronically exposed neurons changed extensively, with some processes ramped up, and others shut down, harmful molecules building up and protective ones depleted, alongside elevated lipid peroxidation. When both groups were then subjected to a further stress, the briefly exposed cells coped, while the chronically exposed cells could not.
“We think these coordinated alterations in iron-handling and antioxidant defence proteins make chronically exposed neurons vulnerable to neurodegenerative pathology,” Dr Dar said. “Entering this state of chronoferroptosis may set neurons up for age-related failure.”
He summed up the central finding plainly: “It’s not the amount of iron that seals the fate of these cells, it’s the amount of time they spend under stress.”
The findings open a door to earlier intervention. If clinicians could one day detect the point at which neurons enter this vulnerable state, it may become possible to correct iron imbalance or restore cellular defences before lasting damage sets in.
Dr Maher noted that her lab is already working on this front: “It’s not something we worked on in this paper, but our lab has developed several compounds to inhibit this pathway. This could really be a promising therapeutic route for boosting neuron resilience and staving off neurodegeneration as we grow older.”
For Jammu and Kashmir, Dr Dar’s role in the discovery carries significance beyond the laboratory. Having trained and built his career to the point of co-leading research at one of the world’s foremost neuroscience institutes, he brings recognition to the region through work that bears directly on diseases affecting families everywhere, including at home in Kashmir.
The study was co-authored by David Soriano-Castell and Dr Pamela Maher of the Salk Institute, and was funded by the US National Institutes of Health.
