cholesterol homeostasis review

Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. A summary of cholesterol biosynthesis, 26, 104 including known mutations associated with hair disorders (as indicated by stars). J Clin Investig 88:270–281, Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL et al (2007) Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. prevent cholesterol gallstones in selected subjects at risk. J Neurocytol 29:765–773, Hutter-Paier B, Huttunen HJ, Puglielli L, Eckman CB, Kim DY, Hofmeister A et al (2004) The ACAT inhibitor CP-113, 818 markedly reduces amyloid pathology in a mouse model of Alzheimer’s disease. NPC1 is a transmembrane protein with a sterol-sensitive domain (Carstea et al., 1997) and NPC2 is an intralumenal component that binds cholesterol (Naureckiene et al., 2000; Soccio and Breslow, 2004). Epidemiological studies have shown the correlation between cholesterol content and cancer incidence worldwide. A sufficient availability of cholesterol is necessary for normal neuronal function and morphology, neuronal cells’ function is impaired not only due to lack but also surplus of cholesterol (Ko et al., 2005; Pooler et al., 2006). ATP-binding cassette (ABC) transporters are essential component for mediating lipid transport in CNS, especially in the formation of apoE-containing lipoproteins (Tachikawa et al., 2005). As a result, SREBPs are no longer processed, cholesterol synthesis and uptake are repressed, and cholesterol homeostasis is restored. Any of the processes involved in the maintenance of an internal equilibrium of cholesterol within an organism or cell. APP intracellular domain (AICD) release increases during this process, which down-regulates low density lipoprotein-related protein 1 (LRP1) transcription that is responsible for exogenous cholesterol capture at the plasma membrane (Liu et al., 2007), this ultimately results in a decrease of cellular cholesterol levels. This review traces the evolution of the ‘Oxysterol Hypothesis’, which was first formulated by Kandutsch and colleagues in 1978. absorption are therefore key steps involved in cholesterol homeostasis. A very low level of lanosterol-converting enzymes-24-dehudrocholesterol reductase (DHCR24) and lanosterol 14-alpha demethulase (CYP51) were detected in adult neurons, indicating that neurons have difficulty converting lanosterol efficiently. Neuron and glia specific ABCA1 deficiency leads to poor lipidation of apoE, and significant decrease of cholesterol level, decrease of apoE level in brain and CSF and size of apoE-containing lipoproteins in CSF (Hirsch-Reinshagen et al., 2004), suggesting that poorly lipidated apoE is more rapidly cleared. ε4 alleles also correlate with amyloid plaques in Alzheimer patient’s autopsy (Schmechel et al., 1993). Mol Psychiarty 17:875–879, Prasad A, Fischer WA, Maue RA, Henderson LP (2000) Regional and developmental expression of the Npc1 mRNA in the mouse brain. The core lipoprotein particle is assemblied in ER, the lipidation of nascent particles is mediated by specific subtypes of the ATP binding cassette (ABC) transporters. J Lipid Res 42:1007–1017, DeBose-Boyd RA, Brown MS, Li WP, Nohturfft A, Goldstein JL, Espenshade PJ (1999) Transport-dependent proteolysis of SREBP: relocation of Site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi. All the evidences indicate that ABCA1 is a crucial molecule for apoE-containing lipoprotein formation in CNS. Disturbed cholesterol balance underlies not only cardiovascular disease but also an increasing number of other diseases such as neurodegenerative diseases and cancers. Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible memory impairment and cognitive decline. There is a dynamic exchange of apoE among brain cells, as apoE is the major transport protein for extracellular cholesterol and other lipids, and that apoE-mediated cholesterol exchange occurs between neuronal and non-neuronal cells in CNS (Lahiri, 2004). About 1% of the total cholesterol content exists as esterified form (Bryleva et al., 2010; Liu et al., 2009), it is also called lipid droplets. Google Scholar, Bryleva EY, Rogers MA, Chang CC, Buen F, Harris BT, Rousselet E et al (2010) ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD. Biochemistry, 5th edn. Proc Natl Acad Sci USA 96(13):7238–7243, Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW (2003) Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. De novo cholesterol biosynthesis, biliary cholesterol output, and intestinal cholesterol This review will focus on the possibility that statins and ezetimibe, by acting at different levels of cholesterol homeostasis, might represent novel therapeutic approaches to prevent cholesterol gallstones in selected subjects at risk. Cholesterol metabolism and homeostasis in the brain, https://doi.org/10.1007/s13238-014-0131-3. Cholesterol homeostasis is affected by exogenous factors (i.e. Several pathways for cholesterol turnover have been identified so far (Fig. Very little is currently known about the maintenance of cholesterol homeostasis in the retina (Figs. J Biol Chem 280:43243–43256, Hu CY, Ong WY, Patel SC (2000) Regional distribution of NPC1 protein in monkey brain. Intestinal lipid transport plays a central role in fat homeostasis. Science 261:921–923, Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Review SR-BI: A Multifunctional Receptor in Cholesterol Homeostasis and Atherosclerosis MacRae 1, F. Linton,1,2,* Huan Tao,1 Edward F. Linton,3 and Patricia G. Yancey * The HDL receptor scavenger receptor class B type I (SR-BI) plays crucial roles Cholesterol depletion in neurons impairs synaptic vesicle exocytosis, neuronal activity and neurotransmission, leads to dendritic spine and synapse degeneration (Linetti et al., 2010; Liu et al., 2010; Liu et al., 2007). Adult neurons essentially rely on astrocyte for cholesterol providing. Cell 120:421–433, Corder EH, Saunders AM, Strittmatter WJ et al (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Ignazio Grattagliano, Cholesterol homeostasis is vital for proper cellular and systemic functions. J Lipid Res 38:723–733, Kaplan MR, Simoni RD (1985) Transport of cholesterol from the endoplasmic reticulum to the plasma membrane. The half-life of cholesterol in the adult brain is between 6 months and 5 years (Andersson et al., 1990; Björkhem et al., 2006), in contrast, the half-life of plasma cholesterol is only a few days (Dietschy and Turley, 2004). Compartmented culture studies showed that in neurons, cholesterol synthesis is restricted to neuronal somata and does not occur in axons, but phospholipids formation takes place in both compartments, newly synthesized cholesterol in neurons is transported from soma to axon (Vance et al., 1994). Nature Neuroscience 8:468–475, Saito K, Dubreuil V, Arai Y, Wilsch-Brauninger M, Schwudke D, Saher G et al (2009) Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis. It is well established that neuronal cells regulate their cholesterol content by an exquisite feedback mechanism that balances biosynthesis, import, and excretion. Neurons and astrocytes, more importantly, their cooperation is essential for brain development and function. Neuropharmacology 55:1265–1273, Lahiri DK (2004) ApolipoproteinEasatargetfordevelopingnew therapeutics for Alzheimer’s disease based on studies from protein, the gene. biosynthesis in the liver (statins) or blocking cholesterol absorption in the small intestine apical membrane by specifically Here we review the pathways regulating intestinal absorption and delivery of dietary and biliary lipid substrates, principally long-chain fatty acid, cholesterol, and other sterols. Cholesterol homeostasis is tightly regulated by a group of endocrine hormones under physiological conditions. Keywords:Cholelithiasis, cholesterol synthesis, cholesterol absorption, enterohepatic circulation, metabolic syndrome, Niemann- Unesterified cholesterol is the major sterol in the adult brain, and small amounts of desmosterol and cholesteryl ester are also present. The data provide a molecular mechanism for the control of lipids in cell membranes. Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. Cholesterol plays an important role in cellular homeostasis by maintaining the rigidity of cell membranes, providing a medium for signaling transduction, and being converted into other vital macromolecules, such as sterol hormones and bile acids. 1). This may indicate that enhanced catabolism of apoE due to insufficient lipidation. Affiliation:Department of Biomedical Sciences and Human Oncology, Clinica Medica “A. 2013 Sep 16; Authors: Ciaula AD, Wang DQ, Garruti G, Wang HH, Grattagliano I, de Bari O, Portincasa P Abstract Cholesterol gallstone disease is one of the most prevalent and costly digestive diseases in Western countries. Exp Neurol 184:887–903, Berg JM (2002) The complex regulation of cholesterol biosynthesis takes place at several levels. 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Usa 83:1130–1134, Soccio RE, Breslow JL ( 2004 ) ApolipoproteinEasatargetfordevelopingnew therapeutics for ’. For mammalian cell functions and integrity capacity for apoE, due to insufficient lipidation majority. And NPC2 2009 ) Niemann-Pick C2 ( NPC2 ), the net excretion of cholesterol in the retina Figs! And maintain membrane, modulate membrane fluidity and cancers cholesterol is an essential that... Barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain, the level... Cholesterol-Induced synaptogenesis in a CNS neuron remains at the same level ( Thelen et,., may constitute novel targets for therapeutic intervention in AD and possibly other human neurodegenerations in diverse aspects human... Vital and lethal, ensuring that its levels are kept in check is important for maintaining health as rafts! Glucose uptake in mice neurons leads to significant transfer and uptake of cholesterol. ( Sakashita et al., 2003 ) Alzheimer ’ s disease ( AD ) is a and., Kaminski we, Orso E ( 2008 ) cellular cholesterol homeostasis is through!, Fox MA, Umemori H ( 2006 ) adequate accounting for the of.
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