Journal
MOLECULAR NEUROBIOLOGY
Volume 32, Issue 1, Pages 89-103Publisher
HUMANA PRESS INC
DOI: 10.1385/MN:32:1:089
Keywords
cyclooxygenases; diacylglycerol kinase epsilon; docosahexaenoic acid; docosanoids; neuroprotection; platelet-activating factor; prostaglandins
Categories
Funding
- NCRR NIH HHS [P20RR16816] Funding Source: Medline
- NEI NIH HHS [EY05121] Funding Source: Medline
- NINDS NIH HHS [NS23002, NS46741] Funding Source: Medline
Ask authors/readers for more resources
The extensive networking of the cells of the nervous system results in large cell membrane surface areas. We now know that neuronal membranes contain phospholipid pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury. These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuroprotection. Prostaglandins are synthesized as a result of cyclooxygenase activity. In the first step of the arachidonic acid cascade, the short-lived precursor, prostaglandin H2, is synthesized. Additional steps in the cascade result in the synthesis of an array of prostaglandins, which participate in numerous physiological and neurological processes. Our laboratory recently reported that the membrane polyunsaturated fatty acid, docosahexaenoic acid, is the precursor of oxygenation products now known as the docosanoids, some of which are powerful counter-proinflammatory mediators. The mediator 10,17S-docosatriene (neuroprotectin D1, NPD1) counteracts leukocyte infiltration, NF-kappa activation, and proinflammatory gene expression in brain ischemia-reperfusion and is an apoptostatic mediator, potently counteracting oxidative stress-triggered apoptotic DNA damage in retinal pigment epithelial cells. NPD1 also upregulates the anti-apoptotic proteins Bc1-2 and Bc1-xL and decreases pro-apoptotic Bax and Bad expression. Another biologically active messenger derived from membrane phospholipids in response to synaptic activity is platelet-activating factor (PAF). The tight regulation of the balance between synthesis (via phospholipases) and degradation (via acetylhydrolases) of PAF modulates the functions of this lipid messenger. Under pathological conditions, this balance is tipped, and PAF becomes a proinflammatory mediator and neurotoxic agent. The newly discovered docosahexaenoic acid signaling pathways, as well as other lipid messengers related to synaptic activation, may lead to the clarification of clinical issues relevant to stroke, age-related macular degeneration, spinal cord injury, Alzheimer's disease, and other diseases that include neuroinflammatory components.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available