Use of Phosphatide Precursors to Promote Synaptogenesis

Wurtman R. J., CANSEV M., Sakamoto T., Ulus I. H.

ANNUAL REVIEW OF NUTRITION, cilt.29, ss.59-87, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 29
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1146/annurev-nutr-080508-141059
  • Dergi Adı: ANNUAL REVIEW OF NUTRITION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.59-87
  • Anahtar Kelimeler: 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
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

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.