The findings suggest that environmental lead exposure may add to the cellular stress
HYDERABAD: Lead exposure could make it harder for nerve cells to clear their own cellular waste, particularly when combined with amyloid‑β peptides, a substance associated with changes seen in neurodegenerative disorders, a study by researchers at the ICMR‑National Institute of Nutrition (ICMR‑NIN) has found.
Published in the Journal of Applied Toxicology, the study offers a glimpse into how an environmental pollutant could interfere with the tiny waste disposal and recycling machinery inside nerve cells. The researchers studied human neuronal cells in the laboratory and examined the effects of lead and two forms of amyloid‑β peptides. They found that while exposure to either lead or amyloid‑β alone caused some disruption, the combination had a much stronger impact on the cells.
The damage centred on lysosomes — tiny structures inside cells that break down damaged proteins and unwanted material and help keep cells functioning normally. Combined exposure reduced cell survival, disrupted the acidic environment required for lysosomes to work and altered their structure.
The researchers also observed changes in proteins and genes involved in maintaining lysosomal health, including TFEB, TRPML1, LAMP1, LAMP2 and Cathepsin B. More concerningly, the lysosomal membranes became unstable and leaky. This could allow destructive enzymes normally contained within the lysosomes to escape into the cell, potentially triggering further cellular damage.
“Our findings show that lead exposure can significantly worsen lysosomal dysfunction in the presence of amyloid‑β,” said Dr Suresh Challa, Scientist‑G and Head, Cell Biology, ICMR‑NIN, who led the research team. “Understanding these cellular changes can help us better understand how environmental exposures may influence neuronal health,” he said.
Dr Bharati Kulkarni, director, ICMR‑NIN, said the findings underline the importance of studying how environmental pollutants interact with biological factors that influence brain health. “Such research can contribute to a better understanding of the pathways involved in neurodegenerative diseases,” she said.
The researchers said the findings suggest that environmental lead exposure may add to the cellular stress associated with amyloid‑β, potentially making nerve cells more vulnerable to damage. However, the study was conducted in human neuronal cells under laboratory conditions, and the findings do not establish that lead exposure directly causes neurodegenerative disease in people.
The study provides further evidence of the need to understand how environmental exposures can interfere with fundamental cellular processes that are essential for maintaining healthy nerve cells.
