Statale: decreased cholesterol in cell membranes promotes neurodegeneration
Lowering the amount of cholesterol in the blood is one of the main strategies adopted to prevent cardiovascular disease, which remains the leading cause of death worldwide. But if the reduction of cholesterol in cell membranes occurs for an extended period of time, it can cause an abnormal accumulation of proteins, leading to the onset of neurodegenerative diseases.
It was discovered by a research team at the University of Milan (“Statale”), led by biologist Caterina La Porta, in a study published in the prestigious international journal “Scientific Reports” of the Nature publishing group. ‘Cholesterol – explained the researchers – plays a crucial role in regulating the properties of cell membranes, especially affecting their fluidity: by regulating the biosynthesis of cholesterol it is possible to affect the form and function of these membranes’.
In general, it is known that the protein neuroserpin promotes brain development and neuronal survival: when mutations occur in the gene encoding this protein, the body produces an abnormal form that tends to aggregate within the neurons, causing abnormal accumulations leading to a rare neurodegenerative disease with symptoms of dementia and epilepsy called “Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB)”.
The Italian researchers observed that the abnormal accumulation of neuroserpin can be related not only to gene mutation but also to prolonged exposure of the cells to substances capable of reducing cholesterol levels in cell membranes, with multiple damage to various physiological processes including the formation of “vesicles”, intracellular structures that carry the different substances useful to the cell, including proteins. By developing a specific mathematical model, the researchers demonstrated that it is the malfunction of the transport system that induces neuroserpin aggregation, even in the absence of gene mutations.
‘Taken together – explained the researches from Milan – our results suggest that long-term treatment with statins (normally used to lower cholesterol - Ed) can induce neuroserpin aggregation, even in the absence of a genetic predisposition. This does not necessarily mean that those treated with statins will develop FENIB. Further studies are needed to clarify this aspect. Certainly, however, protein aggregation is not a normal process; furthermore, neuroserpin is not the only protein that may be affected by decreased cholesterol in cell membranes’.
‘We focused on neuroserpin – added the researchers – but we cannot exclude that the alteration of the membranes and the intracellular transport system may induce the aggregation of other proteins; in addition, neuroserpin aggregation has been associated not only with FENIB, but also with other less rare neurodegenerative diseases, such as Alzheimer’s. We know that decreasing cholesterol levels in the blood can reduce the risk of cardiovascular disease. On the other hand, we still don’t know the consequences of a chronic reduction in cholesterol in cell membranes’.