A reduction in blood cholesterol levels is a key strategy to fight cardiovascular diseases. However, the same cannot be said, if its drastic reduction occurs in cell membranes where it can, instead, cause an abnormal build-up of proteins and the onset of a neurodegenerative disease.
The discovery, which was published in Scientific Reports, was made by a study conducted by Caterina La Porta of the Center for Complexity and Biosystems, the University of Milan, and conducted in partnership with FIRC Institute of Molecular Oncology. The effect of three different statins (simvastatin, rosuvastatin and pravastatin) and of betulin (a compound that interferes with the control of cholesterol levels) was tested in cell cultures.
By resorting to biological experiments and to mathematical simulations, the research team provided evidence that a reduction in the quantity of cholesterol in membranes - achieved both with statins and with betulin - causes the formation of aggregates of a protein called neuroserpin, which is involved in brain development and in the survival of neurons.
Mutations in the gene that encodes neuroserpin lead to the production of an abnormal version of the protein, which is inclined to bind similar compounds, thus forming aggregates within the neurons. These abnormal accumulations, in turn, cause FENIB (familial encephalopathy with neuroserpin inclusion bodies), a very rare hereditary neurodegenerative disease characterised by dementia and seizures.
"We focused on neuroserpin but we cannot rule out the possibility that alterations in membranes and in the intracellular transport system can cause the aggregation of other proteins too", says Caterina La Porta. "Moreover, neuroserpin aggregates have been associated with FENIB and also with other more common neurodegenerative diseases, such as Alzheimer's Disease".
The University of Milan
Department of Biosciences and Center for Complexity and Biosystems
Prof. Caterina La Porta
Tel. 02 503 14927 - 14928
Anna Cavagna - Glenda Mereghetti
Tel. 02 503 12983 - 12025