Wurtman, Richard J.Sakamoto, Toshimasa2021-10-272021-10-272009Wurtman, R. J. vd. (2009). "Use of phosphatide precursors to promote synaptogenesis". Annual Review of Nutrition, 29, 59-87.0199-9885https://doi.org/10.1146/annurev-nutr-080508-141059https://www.annualreviews.org/doi/10.1146/annurev-nutr-080508-141059http://hdl.handle.net/11452/22495New brain synapses form when a postsynaptic structure, the dendritic spine, interacts with a presynaptic terminal. Brain synapses and dendritic spines, membrane-rich structures, are depleted in Alzheimer's disease,as are some circulating compounds needed for synthesizing phosphatides, the major constituents of synaptic membranes. Animals given three of these compounds, all nutrients-uridine, the omega-3 polyunsaturated fatty acid docosahexaenoic acid, and choline-develop increased levels of brain phosphatides and of proteins that are concentrated within synaptic membranes (e.g., PSD-95, synapsin-1), improved cognition, and enhanced neurotransmitter release. The nutrients work by increasing the substrate-saturation of low-affinity enzymes that synthesize the phosphatides. Moreover, uridine and its nucleotide metabolites activate brain P2Y receptors, which control neuronal differentiation and synaptic protein synthesis. A preparation containing these compounds is being tested for treating Alzheimer's disease.eninfo:eu-repo/semantics/closedAccessCognitionAlzheimer's diseasePhosphatideDendritic spineSynaptic membraneP2Y receptorsFatty-acid-compositionCtp-phosphocholine cytidylyltransferasePlasma choline concentrationsPlus docosahexaenoic acidRat sympathetic neuronsBrain-barrier transportAlpha-linolenic acidHamster ovary cellsCdp-cholineAlzheimers-diseaseNutrition & dieteticsAnimaliaAlzheimer diseaseCholineDocosahexaenoic acidsHumansPhospholipidsProdrugsSynapsesSynaptic transmissionUridineArticle0002701186000042-s2.0-6774911167059872919400698Nutrition & dieteticsCholine Phosphate Cytidylyltransferase; Phosphatidylcholines; CiticolineCholineCyanocobalaminDocosahexaenoic acidFolic acidPhospholipidPostsynaptic density protein 95Purinergic P2Y receptorPyridoxineSouvenaidSynapsin IUnclassified drugUridineAlzheimer diseaseClinical trialCognitionDendritic spineDrug effectHumanNerve endingNeurotransmitter releaseNonhumanPhospholipid synthesisPriority journalReviewSynapseSynaptic membraneSynaptogenesis