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Synaptic lipid signaling
Open accessAbstract
Neuronal cellular and intracellular membranes are rich in specialized phospholipids that are reservoirs of lipid messengers released by specific phospholipases and stimulated by neurotransmitters, neurotrophic factors, cytokines, membrane depolarization, ion channel activation, etc. Secretory phospholipases A2 may be both intercellular messengers and generators of lipid messengers. The highly networked nervous system includes cells (e.g., astrocytes, oligodendrocytes, microglial cells, endothelial microvascular cells) that extensively interact with neurons; several lipid messengers participate in these interactions. This review highlights modulation of postsynaptic membrane excitability and long-term synaptic plasticity by cyclooxygenase-2-generated prostaglandin E2, arachidonoyldiacylcylglycerol, and arachidonic acid-containing endocannabinoids. The peroxidation of docosahexaenoic acid (DHA), a critical component of excitable membranes in brain and retina, is promoted by oxidative stress. DHA is also the precursor of enzyme-derived, neuroprotective docosanoids. The phospholipid platelet-activating factor is a retrograde messenger of long-term potentiation, a modulator of glutamate release, and an upregulator of memory formation. Lipid messengers modulate signaling cascades and contribute to cellular differentiation, function, protection, and repair in the nervous system. Lipidomic neurobiology will advance our knowledge of the brain, spinal cord, retina, and peripheral nerve function and diseases that affect them, and new discoveries on networks of signaling in health and disease will likely lead to novel therapeutic interventions.
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“Intracellular processing of the transmembrane glycoprotein βAPP through a sequential β- and γ- secretase–catalyzed proteolysis generates Aβ peptides that are subsequently shuttled to the plasma membrane and secreted (Bazan, 2003; Stein and Johnson, 2003).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Bazan, 2003
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“sAPPα generated via the α-secretase pathway does not give rise to the shorter amyloidogenic Aβ peptides;”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Bazan, 2003
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Self-citation
Metadata
- Authors
- Bazan, N. G.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- Bazan, Nicolas G.
- ORCID
- Bazan, Nicolas G.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 44
- Issue
- 12
- Pages
- 2221-2233
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2168480206
- Cited by
- 247
- References
- 154
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2022: 7 · 2021: 5 · 2020: 13 · 2019: 7 · 2018: 6 · 2017: 6 · 2015: 3 · 2014: 8 · 2013: 12 · 2012: 12
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Eye Institute (R01 EY 05121, R01EY005121)
- National Institute of Neurological Disorders and Stroke (R01NS023002, R01NS23002)
- National Center for Research Resources (P20RR-16816, P20RR016816)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- secretory phospholipase A2, prostaglandin E2, cyclooxygenase-2, endocannabinoids, arachidonic acid, docosanoids, platelet-activating factor, retrograde signaling, long-term potentiation, synaptic plasticity, lipidomics, neuroprotection, astrocytes, microglia, memory formation
- MeSH terms
- Animals, Fatty Acids, Unsaturated, Humans, Nervous System, Synaptic Transmission, Neuronal Plasticity, Platelet Activating Factor, Lipid Metabolism
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