, Volume 153, Issue 3, pp 334-342
Date: 06 Sep 2003

A peptide derived from acetylcholinesterase induces neuronal cell death: characterisation of possible mechanisms

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Acetylcholinesterase (AChE) exhibits functions unrelated to the catalysis of acetylcholine (ACh) in particular during development. Although the underlying mechanism(s) is presently unknown, a candidate peptide fragment (AChE-peptide) has recently been identified, and been shown to induce a continuum of apoptotic and necrotic neuronal cell death in rat hippocampal organotypic cultures. The aim of this study was to trace the cell death pathway initiated by AChE-peptide. Using specific antagonists, it was possible to track a series of cellular events following application of 1 nM AChE-peptide: NMDA receptor activation, opening of the L-type voltage gated calcium channel, activation of calcium/calmodulin kinase II, generation of reactive oxygen species and caspase activation. Pharmacological interception at any stage of this cascade blocked the effect of 1 nM AChE-peptide on neurite retraction. Lactate dehydrogenase (LDH) release, a marker for cell lysis, was unaffected by 1 nM AChE-peptide. In contrast, cell death induced by 1 mM AChE-peptide, monitored as neurite retraction and increased LDH efflux, was not offset by any drug treatment. These data suggest that nanomolar concentrations of AChE-peptide exhibit pathophysiological activity via an apoptotic pathway that could play an important role in neuronal development and neurodegeneration.

Due to an error in the citation line, this revised PDF (published in December 2003) deviates from the printed version, and is the correct and authoritative version of the paper.