Up-regulation of soluble amyloid precursor protein fragment secretion in the rat retina in vivo by metabotropic glutamate receptor stimulation.
Using the novel rat retinal-vitreal model we have investigated the effect of metabotropic glutamate receptor activation on amyloid precursor protein (APP) metabolism. The release of low mol. wt fragments of APP, at 15-23 kDa in particular, was markedly up-regulated by the metabotropic glutamate receptor agonist (1S,3R)-1-amino-1,3-cyclopentane dicarboxylic acid ((1S,3R)-ACPD) in a concentration- and time-dependent manner, and this response was blocked by the receptor antagonist (S)-alpha-methyl-4-caboxyphenylglycine ((S)-MCPG). These results, together with the observation of a lack of deleterious effects of (1S,3R)-ACPD on the retinal neurons, support a physiological role of metabotropic glutamate receptors in mediating the release of soluble APP fragments, an action which may have important functional and therapeutic implications for Alzheimer's disease.
Croucher
Martin J
MJ
Department of Neuroinflammation, Faculty of Medicine, Imperial College London, London, UK. m.croucher@ic.ac.uk
Patel
Hemanshu
H
Walsh
Desmond T
DT
Moncaster
Juliet A
JA
Gentleman
Stephen M
SM
Fazal
Abidali
A
Jen
Ling-Sun
LS
D016564:Amyloid beta-Protein Precursor / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000096:biosynthesis* / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate