Abstract
The mevalonate pathway produces cholesterol and other compounds crucial for numerous cellular processes. It is well known that age and sex modulate this pathway in the liver. Recently, similar effects were also noted in different brain areas, suggesting that alterations of the mevalonate pathway are at the root of marked sex-specific disparities in some neurodevelopmental disorders related to disturbed cholesterol homeostasis. Here, we show how the mevalonate pathway is modulated in a sex-, age- and region-specific manner, and how maternal exposure to exogenous compounds can disturb the regulation of this pathway in the brain, possibly inducing functional alterations.
Highlights
The mevalonate (MVA) pathway produces cholesterol, one of the most important molecules for cellular, tissue, and organism physiology given its crucial structural and metabolic functions.Besides cholesterol, isopentenyl tRNAs, dolichol phosphate, farnesyls, geranylgeranyls, and ubiquinone are produced by the MVA pathway, and these components are crucial for numerous cellular processes such as transcription, protein N-glycosylation, protein prenylation, and mitochondrial electron transport (Figure 1) [1].Cholesterol is one of the main components of the plasma membrane determining its chemicalphysical properties, such as fluidity and stability
Isopentenyl tRNAs, dolichol phosphate, farnesyls, geranylgeranyls, and ubiquinone are produced by the MVA pathway, and these components are crucial for numerous cellular processes such as transcription, protein N-glycosylation, protein prenylation, and mitochondrial electron transport (Figure 1) [1]
The blood–brain barrier (BBB) separates brain cholesterol from theincidence rest of the age-dependent, and this peculiarity may be related to the sex-related of body; cholesterolthe homeostatic controle.g., of this compound in the central nervous system is independent from the dependent pathologies, cardiovascular diseases (CVDs)
Summary
The mevalonate (MVA) pathway produces cholesterol, one of the most important molecules for cellular, tissue, and organism physiology given its crucial structural and metabolic functions. Isopentenyl tRNAs, dolichol phosphate, farnesyls, geranylgeranyls, and ubiquinone are produced by the MVA pathway, and these components are crucial for numerous cellular processes such as transcription, protein N-glycosylation, protein prenylation, and mitochondrial electron transport (Figure 1) [1]. Cholesterol is not uniformly distributed in cell membranes, rather it is concentrated in specialized sphingolipid-rich domains called rafts and caveolae, which are involved in signaling across membranes and are important for cellular functions [2,3]. Imbalanced cholesterol metabolism very often causes pathological changes. It is well-known that cholesterol accumulation at the artery wall is determinant for the pathogenesis of atherosclerosis and cardiovascular diseases (CVDs).
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