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Handbook of Neurochemistry and Molecular Neurobiology pp 311–352Cite as

Metabolism and Functions of Platelet-Activating Factor (PAF) in the Nervous Tissue

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Abstract:

Platelet Activating Factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was first identified as a lipid mediator of inflammation and immunological response. This compound is present at very low concentration in normal mammalian brain where it is synthesized by two distinct pathways. The de novo pathway utilizes 1-alkyl-2-acetyl-sn-glycerol and CDP-choline as substrates of a DTT-insensitive phosphocholine transferase (PAF-PCT). The remodeling pathway requires the production of 1-alkyl-2-lyso-sn-glycero-3-phosphocholine (lysoPAF) produced by the hydrolysis of 1-alkyl-2-(long-chain)acyl-sn-glycero-3-phosphocholine (alkylacylGPC) by the action of phospholipases A2. Alternatively, lysoPAF can be produced by transacylation from alkylacyl-GPC to 1-alk-1'-enyl-2-lyso-sn-glycero-phosphoethanolamine (lysoPlsEtn) produced by a phospholipase A2 as well. LysoPAF is acetylated to PAF by lysoPAF acetyltransferase (lysoPAF-AcT). The relative contribution of the two pathways to PAF synthesis depends on several factors including the concentration of substrates, energy availability, Ca2+ concentration, and phosphorylation state of key enzymes. PAF is transformed into the inactive lysoPAF by PAF acetylhydrolases (PAF-AH). Three intracellular isoforms of PAF-AH have been identified in mammalian brain. In neural cells, PAF is not stored and can be released into the extracellular space. Neural cells possess plasma membrane and intracellular receptors. Plasma membrane receptor (PAFR) has been pharmacologically characterized and cloned. This receptor is expressed in almost all brain areas. Cellular responses to the activation of PAFR are mediated by G-proteins and lead to a complex intracellular signaling. A number of natural and synthetic antagonists of PAFR and intracellular binding sites have been identified. In the brain, PAF participates im physiological mechanisms such as synaptic transmission, long-term potentiation, memory formation, proliferation and differentiation of neural cells, regulation of gene expression, and chemotaxis. Increased levels of PAF, due to upregulation of biosynthetic pathways or to downregulation of PAF-AH, have been observed in pathological conditions such as neuroinflammation, brain ischemia, and neurodegenerative diseases. Relatively high concentration of PAF causes neuronal death by apoptosis, which is linked to the neurotoxic effects of the execessive glutamate release, causing overloading of post-synaptic Ca2+ and the consequent activation of Ca2+-dependent enzymes including PLA2s.

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Abbreviations

acylPAF:

1-acyl-2-(short-chain) acyl-GPC

acyl-DHAP:

1-acyl-DHAP

alkenylacylGPE:

1-alk-1'enyl-2-acyl-GPE

alkylacetylG:

1-alkyl-2-acetyl-sn-glycerol

alkylacylGPC:

1-alkyl-2-(long-chain)acyl-GPC

alkylGP:

1-alkyl-2-lyso-sn-glycero-3-phosphate

AlkylGP-AcT:

alkylGP acetyltransferase

DHAP:

dihydroxyacetone phosphate

GPC:

glycerophosphocholine

GPE:

glycerophosphoethanolamine

lysoPAF:

1-alkyl-2-lyso-GPC

lysoPAF-AcT:

acetyl-CoA:lyso-PAF acetyltransferase

lysoPC:

1-acyl-2-lyso-GPC

mc-PAF:

1-O-alkyl-2-N-methylcarbamyl-GPC

PAF:

platelet activating factor

PAF-AH:

PAF acetyl hydrolase

PAF-PCT:

DTT-insensitive phosphocholinetransferase

PAFR:

PAF plasma membrane receptor

PFPC:

1-hexadecanoyl-2-formyl-glycerophosphocholine

PlsEtn:

ethanolamine plasmalogens

PlsEtn-PLA2 :

plasmalogen-selective PLA2

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Authors
  1. G. Goracci
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  2. M. L. Balestrieri
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  3. V. Nardicchi
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Editor information

Editors and Affiliations

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

    Abel Lajtha (Director) (Director)

  2. Department of Medical Chemistry, Biochemistry and Biotechnology, Via Saldini 50, 20133, Milan, Italy

    Guido Tettamanti

  3. Department of Internal Medicine Section of Biochemistry, University of Perugia, via del Giochetto, 06122, Perugia, Italy

    Gianfrancesco Goracci

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Goracci, G., Balestrieri, M.L., Nardicchi, V. (2009). Metabolism and Functions of Platelet-Activating Factor (PAF) in the Nervous Tissue. In: Lajtha, A., Tettamanti, G., Goracci, G. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30378-9_13

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