Use of phosphatide precursors to promote synaptogenesis.
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.
Wurtman
Richard J
RJ
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. dick@mit.edu
Cansev
Mehmet
M
Sakamoto
Toshimasa
T
Ulus
Ismail H
IH
D000544:Alzheimer Disease / Q000188:drug therapy*; D002794:Choline / Q000008:administration & dosage / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D010743:Phospholipids / Q000378:metabolism / Q000627:therapeutic use*; D011355:Prodrugs / Q000008:administration & dosage* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D014529:Uridine / Q000008:administration & dosage / Q000378:metabolism
D010743:Phospholipids; D011355:Prodrugs; D004281:Docosahexaenoic Acids; D002794:Choline; D014529:Uridine