The onset of brain injury and neurodegeneration triggers the synthesis of docosanoid neuroprotective signaling.
Bioactive lipid messengers are formed through phospholipase-mediated cleavage of specific phospholipids from membrane reservoirs. Effectors that activate the synthesis of lipid messengers, include ion channels, neurotransmitters, membrane depolarization, cytokines, and neurotrophic factors. In turn, lipid messengers regulate and interact with multiple pathways, participating in the development, differentiation, function (e.g., long-term potentiation and memory), protection, and repair of cells of the nervous system. Overall, bioactive lipids participate in the regulation of synaptic function and dysfunction. Platelet-activating factor (PAF) and COX-2-synthesized PGE(2) modulate synaptic plasticity and memory. Oxidative stress disrupts lipid signaling, fosters lipid peroxidation, and initiates and propagates neurodegeneration. Lipid messengers participate in the interactions among neurons, astrocytes, oligodendrocytes, microglia, cells of the microvasculature, and other cells. A conglomerate of interrelated cells comprises the neurovascular unit. Signaling at the neurovascular unit is clearly altered in the early stages of cerebrovascular disease as well as in neurodegenerations. Here we will provide examples of how signaling by lipids regulates critical events essential for neuronal survival. We will highlight a newly identified, DHA-derived messenger, neuroprotectin D1, which attenuates oxidative stress-induced apoptosis. The specificity and potency of this novel docosanoid (neuroprotectin D1) indicate a potentially important target for therapeutic intervention.
Bazan
Nicolas G
NG
LSU Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Sciences Center School of Medicine in New Orleans, New Orleans 70112, USA. nbazan@lsuhsc.edu
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D016923:Cell Death; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000009:adverse effects; D008055:Lipids / Q000737:chemistry / Q000502:physiology; D008954:Models, Biological; D009410:Nerve Degeneration / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction
D005227:Fatty Acids; D018836:Inflammation Mediators; D008055:Lipids; D018696:Neuroprotective Agents; C487679:protectin D1; D004281:Docosahexaenoic Acids; C007547:behenic acid