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Handbook of Neurochemistry and Molecular Neurobiology pp 151–170Cite as

Cholesterol—A Janus-Faced Molecule in the Central Nervous System

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Abstract:

Understanding the role of cholesterol in normal brain function and its involvement in specific neurodegenerative diseases has attracted considerable attention. One general observation is that there are notable differences in the brain cholesterol properties and dynamics as compared with cholesterol outside of the brain. In addition, much of what is known of brain cholesterol is based on studies focusing on the total or bulk amount of cholesterol; however, it is becoming increasingly recognized that cholesterol domains may provide greater insight into the cellular function of cholesterol. This chapter, therefore, examines the role of cholesterol in brain, compares the properties and dynamics of brain and peripheral cholesterol, and describes cholesterol domains and the contribution of cholesterol to brain pathophysiology, with an emphasis on Alzheimer's disease (AD). Attention is also directed at the participation of other compounds in the brain cholesterol biosynthetic pathway, namely isoprenoids and the cholesterol metabolites, oxysterols.

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Abbreviations

AD:

Alzheimer's disease

APP:

amyloid precursor protein

Aβ:

amyloid β-protein

BBB:

blood–brain barrier

CSF:

cerebrospinal fluid

CYP46A1:

cholesterol 24-hydroxylase

DHCR7:

3β-hydroxysterol Δ7-reductase

FPP:

farnesyl pyrophosphate

GGPP:

geranylgeranyl pyrophosphate

GPI:

Glycosylphosphatidylinositol

HD:

Huntington's disease

NPC:

Niemann–Pick type C

P-gp:

P-glycoprotein

LDL:

low-density lipoproteins

LRP:

low-density lipoprotein receptor-related protein

SLOS:

Smith–Lemli–Opitz syndrome

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Acknowledgments

This work was supported by grants from the National Institutes of Health AG-23524, AG-18357, NATO Collaborative Linkage Grant (980136), and resources/facilities of the Minneapolis VA Medical Center.

Authors
  1. W. G. Wood
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  2. U. Igbavboa
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  3. G. P. Eckert
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  4. W. E Müller
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, New York, 10962, Orangeburg, USA

    Abel Lajtha

  2. Department of Psychiatry Millhauser Labs, Room MHL‐HN–604A, New York University School of Medicine, 550 First Avenue, N.Y. 10016, New York, USA

    Maarten E. A. Reith Ph.D.

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Wood, W.G., Igbavboa, U., Eckert, G.P., Müller, W.E. (2007). Cholesterol—A Janus-Faced Molecule in the Central Nervous System. In: Lajtha, A., Reith, M.E.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30380-2_7

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