Metabotropic glutamate receptors regulate APP processing in hippocampal neurons and cortical astrocytes derived from fetal rats.

Abstract:

:It has previously been shown that stimulation of muscarinic m1 or m3 receptors can, by generating diacylglycerol (DAG) and activating protein kinase C (PKC), accelerate the breakdown of the amyloid precursor protein (APP) to form soluble, non-amyloidogenic peptides (APPs). This relationship has been demonstrated in human glioma and neuroblastoma cells as well as in transfected human embryonic kidney (HEK) cells and PC12 cells. We now provide evidence that stimulation of metabotropic glutamate receptors (mGluRs), which also are coupled to DAG and PKC, similarly accelerates processing of APP into non-amyloidogenic APPs in hippocampal neurons and cortical astrocytes derived from normal fetal rats. The mGluR antagonist, L(+)-2-amino-3-phosphonopropionic acid (L-AP3), and GF 109203X, an inhibitor of PKC, both blocked the release of APPs from hippocampal neurons and astrocytes evoked by glutamate receptor stimulation. Inasmuch as glutamatergic neurons in cortex and hippocampus are known to be damaged in Alzheimer's disease, our findings suggest that amyloid formation may be enhanced by the resulting glutamate deficiency and that selective mGluR agonists may be useful in facilitating synaptic efficacy and treating the disease.

journal_name

Ann N Y Acad Sci

authors

Lee RK,Jimenez J,Cox AJ,Wurtman RJ

doi

10.1111/j.1749-6632.1996.tb34443.x

subject

Has Abstract

pub_date

1996-01-17 00:00:00

pages

338-43

eissn

0077-8923

issn

1749-6632

journal_volume

777

pub_type

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