Crosstalk Between Calpain and Calcineurin in Excitotoxic Neurodegeneration; Therapeutic Targets for the Treatment of Excitotoxic Neurodegeneration

Author(s): Hai-Yan Wu, Hideki Matsui, Kazuhito Tomizawa

Journal Name: Current Medicinal Chemistry - Central Nervous System Agents
Continued as Central Nervous System Agents in Medicinal Chemistry

Volume 5 , Issue 3 , 2005


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

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Article Details

Year: 2005
Page: [207 - 216]
Pages: 10
DOI: 10.2174/1568015054863873
Price: $58

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