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E Prostanoid Receptors in Brain Physiology and Disease

  • Reference work entry
Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Here we will review the prostaglandin (PG) pathway with a focus on emerging data that highlight a central role for PGE2 in ischemic injury and several neurodegenerative diseases. PGE2 activates a family of four G protein-coupled receptors, EP1 to EP4, which are expressed throughout the central nervous system on different cell types where they play central roles in physiologic and pathophysiologic responses. Of these, the data most clearly point to EP1 activation as a mediator of neurotoxicity in models of ischemic injury and EP2 activation as a mediator of activated microglial paracrine damage to neurons and a suppressor of microglia phagocytosis of aggregated neurotoxic peptides. Preclinical animal models of some human neurologic diseases support the potential efficacy of targeting specific EP receptor subtypes in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemic stroke. Clinical trials targeting any EP receptor in neurologic disease have not yet been reported.

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Abbreviations

AA:

arachidonic acid

AD:

Alzheimer's disease

ALS:

amyotrophic lateral sclerosis

APP:

amyloid precursor protein

CNS:

central nervous system

COXs:

cyclooxygenases

CRTH2:

chemoattractant receptor homologous molecule expressed on Th2 cells

CSF:

cerebrospinal fluid

DHA:

docosahexaenoic acid

FAD:

Familial Alzheimer's disease

ICAM:

intercellular adhesion molecule

ICV:

intracerebroventricular

iNOS:

inducible nitric oxide synthase

IL-6:

interleukin-6

LGs:

Levuglandins

LOXs:

lipoxygenases

LPS:

lipopolysaccharide

MCP-1:

monocyte chemotactic protein-1

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NMDA:

N-methyl-D-aspartic acid

NSAIDs:

nonsteroidal anti-inflammatory drugs

PD:

Parkinson's disease

PG:

prostaglandin

PL:

phospholipase

PS:

presenilin

ROS:

reactive oxygen species

SOD1:

superoxide dismutase

TNF-α:

tumor necrosis factor-α

Tx:

thromboxane

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Authors
  1. C. D. Keene
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  2. P. J. Cimino
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  3. R. M. Breyer
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  4. K. S. Montine
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  5. T. J. Montine
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Editor information

Editors and Affiliations

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

    Abel Lajtha (Director) (Director)

  2. Institute of Experimental Medicine, Hungarian Academy of Sciences, 43, H-1083 Budapest, Szigony, Hungary

    E. Sylvester Vizi

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Keene, C.D., Cimino, P.J., Breyer, R.M., Montine, K.S., Montine, T.J. (2008). E Prostanoid Receptors in Brain Physiology and Disease. In: Lajtha, A., Vizi, E.S. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30382-6_15

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