HYDERABAD: Exposure to lead may make nerve cells more vulnerable to damage by disrupting their natural waste-clearing system, particularly when combined with amyloid-ß peptides, according to a study by researchers at the ICMR-National Institute of Nutrition (ICMR-NIN).
The study, published in the Journal of Applied Toxicology, examined the effects of lead and two forms of amyloid-ß peptides on human neuronal cells in laboratory conditions.
Nerve cells rely on lysosomes, tiny structures that function as the cell’s waste-disposal and recycling system. They break down damaged proteins and other unwanted material, helping maintain cellular health.
The researchers found that exposure to lead or amyloid-ß separately caused some impairment of lysosomal function. However, when the cells were exposed to both, the damage was substantially greater.
Combined exposure reduced cell survival, disrupted the acidic environment required for normal lysosomal activity and altered the structure of the lysosomes.
The researchers also observed changes in proteins and genes involved in maintaining lysosomal health, including TFEB, TRPML1, LAMP1, LAMP2 and Cathepsin B.
The lysosomal membranes also became unstable and leaky. Such damage could allow harmful enzymes to escape into the cell, potentially triggering further cellular injury.
According to the researchers, the findings suggest that environmental lead exposure could add to the cellular stress associated with amyloid-ß and increase the vulnerability of nerve cells to damage. The findings offer insights into how environmental pollutants may interact with biological factors involved in cellular changes associated with neurodegenerative disorders.
Dr Suresh Challa, Scientist-G and Head, Cell Biology, ICMR-NIN, who led the research team, said, “Our findings show that lead exposure can significantly worsen lysosomal dysfunction in the presence of amyloid-ß. Understanding these cellular changes can help us better understand how environmental exposures may influence neuronal health.”