Srinagar – A Kashmiri-origin scientist working in the United States has helped identify and name a previously unknown cellular process that could reshape scientists’ understanding of how brain cells gradually become vulnerable to neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, offering a potential new avenue for early intervention and treatment.
Dr Nawab John Dar, a postdoctoral researcher at the Salk Institute for Biological Studies in California, is the lead and co-corresponding author of a peer-reviewed study published in Cell Death Discovery that introduces the term “chronoferroptosis”—a chronic cellular stress pathway in which neurones remain alive but progressively lose their resilience over time, making them increasingly susceptible to age-related degeneration.
The study, published on June 18, identifies prolonged iron accumulation inside neurones as a central driver of this newly described biological process and suggests that preventing or reversing it may help delay or mitigate neurodegenerative diseases.
Dr Dar shares corresponding authorship with senior scientist Dr Pamela Maher, Research Professor at the Salk Institute, a globally recognised neuroscience research centre founded by polio vaccine pioneer Jonas Salk.
Neurodegenerative diseases, particularly Alzheimer’s and Parkinson’s, affect millions of people worldwide and have long been associated with abnormal iron accumulation in the brain. However, scientists have struggled to explain why neurones often remain functional for years despite steadily rising iron levels before eventually succumbing to disease.
The new research proposes that the answer lies not in iron itself but in the duration of exposure.
“It isn’t the iron itself that is a problem with age. It is this accumulation of iron over time that is the problem,” Dr Dar said.
To investigate the phenomenon, the researchers developed what they describe as the first progressive laboratory model of chronic iron accumulation in human-derived neuronal cells. Unlike earlier experiments that typically exposed cells to iron for only 24 to 48 hours, the team compared acute exposure lasting six to eight hours with sustained exposure over nine days using identical iron concentrations.
Their findings revealed striking differences.
While briefly exposed neurones showed little biochemical disruption and remained capable of handling subsequent stress, chronically exposed neurones underwent widespread metabolic and molecular changes. Protective antioxidant systems weakened, harmful lipid peroxidation increased, and proteins responsible for maintaining iron balance became dysregulated, leaving the cells significantly more vulnerable.
The researchers concluded that neurones can enter a prolonged state of chronic stress without immediately dying—a condition they have termed “chronoferroptosis”.
“We think these coordinated alterations in iron-handling and antioxidant defence proteins make chronically exposed neurones vulnerable to neurodegenerative pathology. Entering this state of chronoferroptosis may set neurones up for age-related failure,” Dr Dar said.
The study builds upon decades of research into ferroptosis, previously understood primarily as an iron-dependent form of programmed cell death driven by oxidative damage to cellular lipids.
According to Dr Maher, the new findings substantially expand that understanding.
Instead of representing only a pathway leading directly to cell death, ferroptosis may also exist as a persistent stress response that gradually weakens neurones long before irreversible degeneration occurs.
Researchers believe this discovery could have significant implications for future therapies.
By identifying the onset of chronoferroptosis before neurones begin dying, scientists may eventually be able to intervene with treatments that restore iron balance, strengthen antioxidant defences and preserve neuronal resilience.
“It’s not the amount of iron that seals the fate of these cells; it’s the amount of time they spend under stress,” Dr Dar said, underscoring the importance of duration rather than quantity in determining neuronal vulnerability.
Although therapeutic interventions were not evaluated in the present study, the researchers noted that the Salk Institute has already developed several experimental compounds aimed at inhibiting the newly identified pathway.
“This could really be a promising therapeutic route for boosting neurone resilience and staving off neurodegeneration as we grow older,” Dr Maher said.
For Jammu and Kashmir, the publication marks a significant scientific milestone.
Originally from Kashmir Valley, Dr Dar’s role as lead and co-corresponding author reflects a notable contribution by a researcher from the region to frontline international neuroscience. His work addresses one of the most pressing challenges in ageing research and neurological medicine while bringing global recognition to Kashmiri scientific talent.
The research was co-authored by David Soriano-Castell and Dr Pamela Maher at the Salk Institute and was supported by grants from the US National Institutes of Health.
The paper, titled “Sustained Dysregulation of Iron and Glutathione Homeostasis Induces Chronoferroptosis, a Persistent Ferroptotic Adaptation in Neuronal Cells”, was published in Cell Death Discovery and has since attracted attention from several international scientific and medical publications.
This article has been automatically published using a syndicated feed. The content is sourced externally and may not have been reviewed by The Freelancers Team.
