Use of phosphatide precursors to promote synaptogenesis

Annu Rev Nutr. 2009:29:59-87. doi: 10.1146/annurev-nutr-080508-141059.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Choline / administration & dosage
  • Choline / metabolism
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / metabolism
  • Humans
  • Phospholipids / metabolism
  • Phospholipids / therapeutic use*
  • Prodrugs / administration & dosage*
  • Prodrugs / metabolism
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects
  • Uridine / administration & dosage
  • Uridine / metabolism


  • Phospholipids
  • Prodrugs
  • Docosahexaenoic Acids
  • Choline
  • Uridine