New Delhi, Feb 9: Researchers have outlined a sequence of events that can lead to Parkinson’s disease, including disruptions to lipid mechanisms.
The team, led by researchers at the US’ Baylor College of Medicine and Duncan Neurological Research Institute, focused on a common Parkinson’s risk gene called ‘SPTSSB’, which also helps regulate the first steps in the production of sphingolipids — involved in cell-cell interaction, cell proliferation and migration, and cell death.
They studied a variant of the gene SPTSSB, known as ‘rs1450522’, linked to an increased risk of developing the neurodegenerative condition.
“We studied blood samples of people carrying this genetic variant who were healthy — they did not show any symptoms of the condition, like tremors, limb stiffness, gait and balance problems,” author Dr Joshua Shulman, professor of neurology, neuroscience and molecular and human genetics at Baylor College of Medicine, said.
The author said that when compared to individuals not carrying the variant ‘rs1450522’, it increases the amount of protein SPTSSB produced in the brain, especially in neurons, and the levels of sphingolipids in the blood.
“Out of 62 sphingolipids that we measured, 23 per cent were significantly altered,” Shulman added.
Furthermore, researchers analysed metabolites in blood samples, such as fatty acids, of 149 people with the neurological condition and 150 people without it, to identify biological substances, or biomarkers, that may mediate Parkinson’s risk.
“We identified multiple other lipids that were altered in patients with Parkinson’s disease. For instance, fatty acids were present at lower levels in patients than in people without the condition. Interestingly, healthy individuals carrying the SPTSSB variant who had higher levels of multiple sphingolipids in blood also had lower levels of certain fatty acids,” Shulman said.
Studies have shown that Parkinson’s susceptibility genes participate in lipid metabolism, and disrupting certain lipid functions may directly promote brain changes linked to the disease’s onset and progression.
The study’s findings were validated using a dataset of thousands of individuals – the gene variant rs1450522 increases Parkinson’s risk, higher levels of SPTSSB protein and an altered lipid metabolism, the researchers said.
The authors wrote, “Our results identify promising biomarkers and reveal a causal chain linking genetic variation to altered gene/protein expression, lipid dysmetabolism, and the manifestation of PD (Parkinson’s disease).” This provides for the first time strong evidence supporting that this chain of events connecting genetic changes and alterations in lipid metabolism may cause Parkinson’s disease, the team said.
While changes in lipid levels were “modest”, Shulman said, “we think they are important primarily because they give us insights into a mechanism, a process that triggers and sustains the condition.” “Understanding how these lipid metabolic changes set the path to Parkinson’s disease can guide the development of treatments to prevent or delay the onset of symptoms,” Shulman said. (PTI)
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