The docosanoid neuroprotectin D1 induces homeostatic regulation of neuroinflammation and cell survival

Significant advancements in our understanding of cell-survival signalling in AD (Alzheimer's disease) stem from recent investigations into the metabolism, trafficking and fate of the essential ω-3 fatty acid DHA (docosahexaenoic acid) (C22:6, n=3). Brain synaptic terminals and neuronal plasma membranes are highly enriched in DHA, and deficiencies in this polyunsaturated fatty acid are characteristic of AD-affected brain. Oxidative stress, targeting phospholipids containing DHA, and age-related DHA depletion are associated with the progressive erosion of normal cognitive function in AD. Current studies support the idea that DHA itself and novel DHA-derived neural synapse- and membrane-derived lipid messengers have considerable potential to modulate cell survival signalling in stressed cultured neural cell models in vitro and in mammalian models of learning, memory and AD in vivo. Key players in this intrinsic rescue system include the α-secretase-processed neurotrophin sAPPα [soluble APPα (amyloid precursor protein α)] peptide, the DHA-derived 10,17S-docosatriene NPD1 (neuroprotectin D1), a tandem brain cytosolic phospholipase A2 and 15-lipoxygenase enzymatic system that biosynthesizes NPD1, and a small family of anti-apoptotic neuroprotective genes that encode Bcl-2, Bcl-XL and Bfl-1 (A1). This paper reviews current ideas regarding DHA and the oxygenated DHA derivative NPD1, intrinsically triggered biolipid neuroprotectants that along with their associated rescue pathways, contribute to life-or-death decisions of brain cells during homoeostasis, aging and neurodegenerative disease.

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Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection

Prostaglandins Leukotrienes and Essential Fatty Acids ◽

10.1016/j.plefa.2009.05.024 ◽

2009 ◽

Vol 81 (2-3) ◽

pp. 205-211 ◽

Cited By ~ 105

Author(s):

Nicolas G. Bazan

Keyword(s):

Docosahexaenoic Acid ◽

Cell Survival ◽

Photoreceptor Cell ◽

Brain Protection ◽

Neuroprotectin D1 ◽

Molecular Events

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The Response of Testes Cells to Low Level, Single dose Helium Particle Irradiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053929 ◽

1982 ◽

Vol 40 ◽

pp. 252-253

Author(s):

D.E. Philpott ◽

W. Sapp ◽

C. Williams ◽

J. Stevenson ◽

S. Black ◽

...

Keyword(s):

Stem Cell ◽

Single Dose ◽

B Cell ◽

Cell Survival ◽

Spermatogonial Stem Cell ◽

Low Doses ◽

Particle Irradiation ◽

Stem Cell Survival ◽

Irradiation Injury ◽

Radio Sensitivity

Spermatogonial stem-cell survival after irradiation injury has been studied in rodents by histological counts of surviving cells. Many studies, including previous work from our laboratory, show that the spermatogonial population demonstrates a heterogeneous response to irradiation. The spermatogonia increase in radio-sensitivity as differentiation proceeds through the sequence As - Apr - A1 - A2 - A3 - A4 - In - B. The stem (As) cell is the most resistant and the B cell is the most sensitive. The purpose of this work is to investigate the response of spermatogonial cell to low doses (less than 10 0 rads) of helium particle irradiation.

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