Cholesterol: Its Regulation and Role in Central Nervous System Disorders

Abstract

Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer's disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules). We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

Canonical microRNAs Enable Differentiation, Protect Against DNA Damage, and Promote Cholesterol Biosynthesis in Neural Stem Cells

“…Because of the blood-brain barrier, brain cholesterol is primarily synthesized de novo and is generally considered as distinct from cholesterol of periphery organs [5,7]. Biosynthesis of cholesterol is through the isoprenoid pathway, which involves more than twenty enzymes [48].…”

“…Cholesterol is an essential structural component of cellular membranes and a precursor for biosynthesis of steroid hormones, oxysterols, and bile acids [5]. In the nervous system, cholesterol is also essential for the formation of myelin, the oligodendrocyte-derived insulating layer that enwraps axons and enables saltatory conduction [5].…”

“…In the nervous system, cholesterol is also essential for the formation of myelin, the oligodendrocyte-derived insulating layer that enwraps axons and enables saltatory conduction [5]. Dysregulation of cholesterol leads to various nervous system disorders such as Alzheimer's disease, Smith-Lemli-Optiz syndrome, and Niemann-Pick Type C disease [6].…”

Selenium supplementation into diets containing carnosic acid, fish and rapeseed oils affects the chemical profile of whole blood in lambs

“…In blood the two thirds of cholesterol is in the esterified form and transferred through bloodstream in small compounds called lipoproteins containing outer shell (built by phospholipid, cholesterol and apolipoproteins) and core containing lipids molecules (Orth and Bellosta, 2012). Ruminants utilize cholesterol for the biosynthesis of hormones, vitamin D and substances that contribute in nutrients digestion.…”

Improvement in clinical laboratory services: approaches to adding value

“…It is obvious, that -rather unpredictable -some "innocent" genetic markers used for lifestyle purpose to a later point in time might become strong genetic markers with severe health implications for the patient and even his relatives. Examples are the epsilon3 and epsilon4 genotypes of APOE, which have only very little effects on lipoprotein metabolism [6] but became one of the most important markers for Alzheimer's disease [7]. Laboratory setting Laboratory testing can be performed in different settings: The conventional testing is performed in medical laboratories, some testing is performed as POCT (point of care testing).…”