A by-product of cholesterol plays a “pivotal” role in Parkinson’s disease, according to new research. The metabolite is critical in the development of the neurodegenerative condition in mice, say Chinese scientists.Their study shows that the by-product, called Hydrocholesterol 24-OHC or 24-OHC, is responsible for the formation of Lewy bodies and the death of dopaminergic neurons in the brain – the two major hallmarks of Parkinson’s disease.
Preventing cholesterol from being converted to 24-OHC might be an effective treatment for Parkinson’s, according to the findings published in the journal PLOS Biology. Study leader Professor Zhentao Zhang, of Wuhan University, says blocking its activity or preventing it from being made by the body could be an effective way of treating Parkinson’s.
Prof Zhang said: “Parkinson’s disease develops when the protein alpha-Syn forms clumps of tiny pathological fibres in the brain called Lewy bodies, which spread from brain cell to brain cell, and eventually trigger the death of dopamine neurons.”
The new study focused on what causes the spread of pathological alpha-Syn, with the researchers suspecting that the culprit was 24-OHC, a cholesterol metabolite known to present at high levels in the brains of people with Parkinson’s disease, and which increases with age. After confirming that 24-OHC levels were higher in the blood of Parkinson’s disease patients as well as in a mouse model of the disease, the research team blocked its production in the mouse model by knocking out the enzyme that creates it from cholesterol.
Prof Zhang said: “This reduced both the spread of the harmful alpha-Syn fibres and the damage to the dopamine neurons in the critical part of the brain. Further experiments with neurons cultured in a dish showed that the addition of 24-OHC caused normal alpha-Syn to change into harmful alpha-Syn fibres.
“Injecting mice with these fibres led to greater spread of Lewy bodies, more dopaminergic neuron degeneration, and greater motor deficits than did injecting them with alpha-Syn fibres formed in the absence of 24-OHC.”
He added: “Drugs that prevent cholesterol from being converted to 24-OHC might therefore be an effective treatment for the disease.”