Molecular Neurobiology

, Volume 41, Issue 2–3, pp 367–374 | Cite as

Omega-3 Essential Fatty Acids Modulate Initiation and Progression of Neurodegenerative Disease

Article

Abstract

The significance of the selective enrichment in omega-3 essential fatty acids in photoreceptors and synaptic membranes of the nervous system has remained, until recently, incompletely understood. While studying mechanisms of cell survival in neural degeneration, we discovered a docosanoid synthesized from unesterified docosahexaenoic acid (DHA) by a 15-lipoxygenase (15-LOX), which we called neuroprotectin D1 (NPD1; 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15E,19Z hexaenoic acid). This lipid mediator is a docosanoid because it is derived from the 22 carbon (22C) precursor DHA, unlike eicosanoids, which are derived from the 20 carbon (20C) arachidonic acid (AA) family member of essential fatty acids. We discovered that NPD1 is promptly made in response to oxidative stress, as a response to brain ischemia–reperfusion, and in the presence of neurotrophins. NPD1 is neuroprotective in experimental brain damage, in oxidative-stressed retinal pigment epithelial (RPE) cells, and in human brain cells exposed to amyloid-β (Aβ) peptides. We thus envision NPD1 as a protective sentinel, one of the very first defenses activated when cell homeostasis is threatened by imbalances in normal neural function. We provide here, in three sections, recent experimental examples that highlight the specificity and potency of NPD1 spanning beneficial bioactivity during initiation and early progression of neurodegeneration: (1) during retinal signal phototransduction, (2) during brain ischemia–reperfusion, and (3) in Alzheimer's disease (AD) and stressed human brain cell models of AD. From this experimental evidence, we conclude that DHA-derived NPD1 regulation targets upstream events of brain cell apoptosis, as well as neuro-inflammatory signaling, promoting and maintaining cellular homeostasis, and restoring neural and retinal cell integrity.

Keywords

Aging Amyloid beta (Aβ) peptide Beta-amyloid precursor protein (βAPP) Cyclooxygenase-2 (COX-2) Docosahexaenoic acid (DHA) Hydroxynonenol (HNE) Neuroprotectin D1 (NPD1) Phospholipase A2 Polyunsaturated fatty acid (PUFA) 

Abbreviations

Aβ42

amyloid beta 42 amino acid peptide

AA

arachidonic acid

ADAM

a disintegrin and metalloprotease

AD

Alzheimer's disease

ALA

α-linolenic acid

ApoE4

apolipoprotein E4 allele

BACE

β-amyloid cleavage enzyme

βAPP

beta-amyloid precursor protein

COX-2

inducible cyclooxygenase-2

cPLA2

cytosolic phospholipase A2

DHA

docosahexaenoic acid

EPA

eicosapentanoic acid

HETE

hydroxyeicosatetraenoic acids

HNE

hydroxynonenal

LOX

lipoxygenase

LPX

lipoxins

LTR

leukotrienes

NFT

neurofibrillary tangles

NPD1

neuroprotectin D1

NVU

neurovascular unit

PG

prostaglandin

PLA2

phospholipase A2

POS

photoreceptor outer segment

PUFA

polyunsaturated fatty acid

ROS

reactive oxygen species

RPE

retinal pigment epithelial

SP

senile plaque

sAPPα

soluble amyloid precursor protein alpha fragment

TNFAIP2

tumor necrosis factor alpha inducible protein-2 (B94)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Diater LaboratoriosMadridSpain
  2. 2.LSU Neuroscience Center of Excellence and Department of OphthalmologyLouisiana State University Health Sciences CenterNew OrleansUSA

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