Abstract
The accumulation of high local concentrations of excitatory amino acids, particularly glutamate, is involved in neuronal cell death in neurodegenerative diseases such as stroke, trauma, Huntingtons disease, and amyotrophic lateral sclerosis. Accumulation of glutamate leads to excessive Ca2+ influx into the neuron. The molecules involved in neuronal degeneration following intracellular Ca2+ overload have been identified. Calcineurin and calpain, a Ca2+/calmodulindependent protein phosphatase and Ca2+-dependent cysteine protease, respectively, are two of the most important Ca2+- dependent effectors during neuronal degeneration. These two molecules have been thought to mediate neuronal degeneration through independent cascades. However, recent studies have shown that a cross-talk pathway exists between calcineurin and calpain in neurons and the pathway plays a critical role in excitotoxic neuronal degeneration. This review covers recent findings regarding the cross-talk pathway involved in neuronal degeneration and novel neuroprotective reagents that block the signal pathway.
Keywords: neuronal degeneration, calpain, calcineurin, neuronal apoptosis, alzheimers disease
Current Medicinal Chemistry - Central Nervous System Agents
Title: Crosstalk Between Calpain and Calcineurin in Excitotoxic Neurodegeneration; Therapeutic Targets for the Treatment of Excitotoxic Neurodegeneration
Volume: 5 Issue: 3
Author(s): Hai-Yan Wu, Hideki Matsui and Kazuhito Tomizawa
Affiliation:
Keywords: neuronal degeneration, calpain, calcineurin, neuronal apoptosis, alzheimers disease
Abstract: The accumulation of high local concentrations of excitatory amino acids, particularly glutamate, is involved in neuronal cell death in neurodegenerative diseases such as stroke, trauma, Huntingtons disease, and amyotrophic lateral sclerosis. Accumulation of glutamate leads to excessive Ca2+ influx into the neuron. The molecules involved in neuronal degeneration following intracellular Ca2+ overload have been identified. Calcineurin and calpain, a Ca2+/calmodulindependent protein phosphatase and Ca2+-dependent cysteine protease, respectively, are two of the most important Ca2+- dependent effectors during neuronal degeneration. These two molecules have been thought to mediate neuronal degeneration through independent cascades. However, recent studies have shown that a cross-talk pathway exists between calcineurin and calpain in neurons and the pathway plays a critical role in excitotoxic neuronal degeneration. This review covers recent findings regarding the cross-talk pathway involved in neuronal degeneration and novel neuroprotective reagents that block the signal pathway.
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Cite this article as:
Wu Hai-Yan, Matsui Hideki and Tomizawa Kazuhito, Crosstalk Between Calpain and Calcineurin in Excitotoxic Neurodegeneration; Therapeutic Targets for the Treatment of Excitotoxic Neurodegeneration, Current Medicinal Chemistry - Central Nervous System Agents 2005; 5 (3) . https://dx.doi.org/10.2174/1568015054863873
DOI https://dx.doi.org/10.2174/1568015054863873 |
Print ISSN 1568-0150 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6158 |
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