Secreted form of amyloid precursor protein enhances basal glucose and glutamate transport and protects against oxidative impairment of glucose and glutamate transport in synaptosomes by a cyclic GMP-mediated mechanism

Mark P. Mattson, Zhi Hong Guo, Jonathan D. Geiger

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Synaptic dysfunction and degeneration are believed to underlie the cognitive deficits that characterize Alzheimer's disease, and overactivation of glutamate receptors under conditions of increased oxidative stress and metabolic compromise may contribute to the neurodegenerative process in many different disorders. The secreted form of amyloid precursor protein (sAPPα), which is released from neurons in an activity-dependent manner, can modulate neurite outgrowth, synaptic plasticity, and neuron survival. We now report that sAPPα can enhance glucose and glutamate transport in synaptic compartments. Treatment of cortical synaptosomes with nanomolar concentrations of sAPPα resulted in an attenuation of impairment of glutamate and glucose transport induced by exposure to amyloid β-peptide and Fe2+. The protective effect of sAPPα was mimicked by treatment with 8- bromo-cyclic GMP and blocked by a cyclic GMP-dependent protein kinase inhibitor, suggesting that protective action of sAPPα is mediated by cyclic GMP. Our data suggest that glucose and glutamate transport can be regulated locally at the level of the synapse and further suggest important roles for sAPPα and cyclic GMP in modulating synaptic physiology under normal and pathophysiological conditions.

Original languageEnglish (US)
Pages (from-to)532-537
Number of pages6
JournalJournal of Neurochemistry
Volume73
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Alzheimer's disease
  • Amyloid β-peptide
  • Apoptosis
  • Excitotoxicity
  • Lipid peroxidation
  • Synapse

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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