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NeuroMolecular Medicine

, Volume 12, Issue 2, pp 133–148 | Cite as

Phospholipases A2 and Inflammatory Responses in the Central Nervous System

  • Grace Y. Sun
  • Phullara B. Shelat
  • Michael B. Jensen
  • Yan He
  • Albert Y. Sun
  • Agnes Simonyi
REVIEW PAPER

Abstract

Phospholipases A2 (PLA2s) belong to a superfamily of enzymes responsible for hydrolyzing the sn-2 fatty acids of membrane phospholipids. These enzymes are known to play multiple roles for maintenance of membrane phospholipid homeostasis and for production of a variety of lipid mediators. Over 20 different types of PLA2s are present in the mammalian cells, and in snake and bee venom. Despite their common function in hydrolyzing fatty acids of phospholipids, they are diversely encoded by a number of genes and express proteins that are regulated by different mechanisms. Recent studies have focused on the group IV calcium-dependent cytosolic cPLA2, the group VI calcium-independent iPLA2, and the group II small molecule secretory sPLA2. In the central nervous system (CNS), these PLA2s are distributed among neurons and glial cells. Although the physiological role of these PLA2s in regulating neural cell function has not yet been clearly elucidated, there is increasing evidence for their involvement in receptor signaling and transcriptional pathways that link oxidative events to inflammatory responses that underline many neurodegenerative diseases. Recent studies also reveal an important role of cPLA2 in modulating neuronal excitatory functions, sPLA2 in the inflammatory responses, and iPLA2 with childhood neurologic disorders associated with brain iron accumulation. The goal for this review is to better understand the structure and function of these PLA2s and to highlight specific types of PLA2s and their cross-talk mechanisms in these inflammatory responses under physiological and pathological conditions in the CNS.

Keywords

Cytosolic phospholipases A2 Calcium-independent phospholipases A2 Secretory phospholipases A2 NADPH oxidase NMDA receptor Inflammatory responses Cerebral ischemia Cytokines Alzheimer’s disease 

Abbreviations

AD

Alzheimer’s disease

APP

Amyloid precursor protein

AA

Arachidonic acid

BEL

Bromoenol lactone

CaMKII

Ca2+/Calmodulin-dependent protein kinase II

CNS

Central nervous system

CSF

Cerebrospinal fluid

COX-2

Cyclooxygenase-2

DHA

Docosahexaenoic acid

ERK

Extracellular signal-regulated kinases

HNE

4-Hydroxynonenal

hsp90

Heat shock protein 90

iNOS

Inducible nitric oxide synthase

IFNγ

Interferon-γ

IL-1β

Interleukin 1β

INAD

Infantile neuroaxonal dystrophy

LPS

Lipopolysaccharide

MAPK

Mitogen-activated protein kinase

MNK1

MAPK-interacting kinase

MRI

Magnetic resonance imaging

NBIA

Idiopathic neurodegeneration with brain iron accumulation

NMDA

N-Methyl-d-aspartic acid

NO

Nitric oxide

NPD1

Neuroprotectin 1

PACOCF3

Palmitoyl trifluoromethyl ketone

PIP2

Phosphatidylinositol-4,5-bisphosphate

PGE2

prostglandin E2

PKC

Protein kinase C

PLA2

Phospholipases A2

SMase

sphingomyelinase

ROS

Reactive oxygen species

TBHP

tert-Butylhydroperoxide

TNFα

Tumor necrosis factor-alpha

Notes

Acknowledgment

This study was supported by P01 AG018357 from NIH.

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Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Grace Y. Sun
    • 1
    • 2
  • Phullara B. Shelat
    • 1
  • Michael B. Jensen
    • 1
  • Yan He
    • 1
  • Albert Y. Sun
    • 2
  • Agnes Simonyi
    • 1
  1. 1.Department of BiochemistryUniversity of MissouriColumbiaUSA
  2. 2.Department of Pathology and Anatomical SciencesUniversity of MissouriColumbiaUSA

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