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 language | English (US) |
|---|---|
| Pages (from-to) | 532-537 |
| Number of pages | 6 |
| Journal | Journal of Neurochemistry |
| Volume | 73 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1999 |
| Externally published | Yes |
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Keywords
- Alzheimer's disease
- Amyloid β-peptide
- Apoptosis
- Excitotoxicity
- Lipid peroxidation
- Synapse
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
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. / Mattson, Mark P.; Guo, Zhi Hong; Geiger, Jonathan D.
In: Journal of Neurochemistry, Vol. 73, No. 2, 1999, p. 532-537.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Mattson, Mark P.
AU - Guo, Zhi Hong
AU - Geiger, Jonathan D.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid β-peptide
KW - Apoptosis
KW - Excitotoxicity
KW - Lipid peroxidation
KW - Synapse
UR - http://www.scopus.com/inward/record.url?scp=0344483869&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344483869&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1999.0730532.x
DO - 10.1046/j.1471-4159.1999.0730532.x
M3 - Article
C2 - 10428048
AN - SCOPUS:0344483869
VL - 73
SP - 532
EP - 537
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -