HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Signal transduction mechanisms in Alzheimer disease.

Abstract
The present article focuses on our studies on the metabolism of the inositol phospholipids in Alzheimer disease (AD). The phospholipase C (PLC) isozyme, PLC-delta 1, was abnormally accumulated in neurofibrillary tangles (NFT), the neurites surrounding senile plaque cores, and neuropil threads in AD brains. Anti-PLC-delta 1 antibody marked the same NFT-bearing neurons containing tau immunoreactivity. Electron microscopic immunocytochemistry revealed that antigenic determinants unique to PLC-delta 1 are mainly present intraneuronally on the amorphous granular components of NFT as well as the abnormal filaments. Although the concentration of PLC-delta 1 protein was significantly higher in the cytosolic fraction of AD cortical tissue than in control brains, the specific activity of PLC-delta 1 is decreased in AD brains. The amounts of PLC-beta 1 and -gamma 1 and type beta protein kinase C were significantly reduced in the membranous fraction of the AD temporal cortical tissues compared with controls. The PLC-delta 1 abnormality was also present in nonneuronal tissues as well as the brains of patients with AD. It was revealed that nitric oxide (NO) formation secondary to Ca2+ influx by N-methyl-D-aspartate (NMDA) receptor activation leads to modifications of PLC-delta 1 similar to those seen in AD brains. These results suggest that altered Ca2+ homeostasis, occurring as a consequence of aberrant phosphoinositide metabolism, may be related to key features of AD such as neurofibrillary degeneration, aberrant amyloid deposits, and neuronal death.
AuthorsS Shimohama, H Matsushima
JournalAlzheimer disease and associated disorders (Alzheimer Dis Assoc Disord) Vol. 9 Suppl 2 Pg. 15-22 ( 1995) ISSN: 0893-0341 [Print] United States
PMID8534418 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Phosphatidylinositols
  • Protein Kinase C
Topics
  • Alzheimer Disease (metabolism)
  • Cell Death
  • Humans
  • Lipid Metabolism
  • Neurofibrillary Tangles
  • Phosphatidylinositols (metabolism)
  • Protein Kinase C (metabolism)
  • Signal Transduction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: