Use of phosphatide precursors to promote synaptogenesis
Date
2009
Authors
Wurtman, Richard J.
Sakamoto, Toshimasa
Journal Title
Journal ISSN
Volume Title
Publisher
Annual Reviews
Abstract
New 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.
Description
Keywords
Cognition, Alzheimer's disease, Phosphatide, Dendritic spine, Synaptic membrane, P2Y receptors, Fatty-acid-composition, Ctp-phosphocholine cytidylyltransferase, Plasma choline concentrations, Plus docosahexaenoic acid, Rat sympathetic neurons, Brain-barrier transport, Alpha-linolenic acid, Hamster ovary cells, Cdp-choline, Alzheimers-disease, Nutrition & dietetics, Animalia
Citation
Wurtman, R. J. vd. (2009). "Use of phosphatide precursors to promote synaptogenesis". Annual Review of Nutrition, 29, 59-87.