Cholesterol Homeostasis Imbalance and Brain Functioning: Neurological Disorders and Behavioral Consequences

Abstract

Cholesterol is an amphipathic sterol compound that exerts both structural and physiological tasks in the plasma membrane of all eukaryotic cells. The planar and rigid structure of this molecule regulates the fluidity of the phospholipid bilayer and its permeability to solutes and ions. The structural role of cholesterol is particularly relevant in the central nervous system, where it represents one of the major components of myelin sheaths, and an important constituent of the synaptic vesicle membranes. The synthesis and trafficking of cholesterol is highly specialized in the brain, and displays several differences if compared to its metabolism in other tissues. In humans, disruption to cholesterol homeostasis can lead to a wide spectrum of pathological conditions. The relevance of this compound in the pathogenesis of atherosclerosis and other cardiovascular diseases is nowadays well established, while correlations existing between cholesterol and brain disorders are still poorly characterized. Therefore, the aim of this review is to summarize the current knowledge that links alterations of cholesterol homeostasis with the onset and the progression of several neurological and neuropsychiatric disorders.