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Cholesterol impairment contributes to neuroserpin aggregation (2017-03-19)

Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimerís and Parkinsonís diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB).

FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER).

Researchers have shown that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol regulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins.

These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation.

Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model.

Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations.

The new mechanism researchers uncovered could be relevant also for other neurodegenerative diseases associated with protein aggregation.

See also:

Fat influences production and survival of brain cells (2013-01-02)

Study finds link between commonly prescribed statin and memory impairment (2013-10-17)

Parkinsonís Protein May Regulate Fat Metabolism (20/01/2012)

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Cholesterol impairment contributes to neuroserpin aggregation

Universitŗ degli studi di Milano