Open AccessInvolvement of Calpain Activation in Neurodegenerative Processes
Author(s) -
Camins Antoni,
Verdaguer Ester,
Folch Jaume,
Pallàs Mercè
Publication year - 2006
Publication title -
cns drug reviews
Language(s) - English
Resource type - Journals
eISSN - 1527-3458
pISSN - 1080-563X
DOI - 10.1111/j.1527-3458.2006.00135.x
Subject(s) - calpain , proteases , neurodegeneration , neuroscience , programmed cell death , caspase , cyclin dependent kinase 5 , neurotoxicity , neuroprotection , biology , microbiology and biotechnology , apoptosis , pharmacology , medicine , signal transduction , biochemistry , disease , enzyme , pathology , toxicity , mitogen activated protein kinase kinase , protein kinase c
One of the challenges in the coming years will be to better understand the mechanisms of neuronal cell death with the objective of developing adequate drugs for the treatment of neurodegenerative disorders. Caspases and calpains are among the best‐characterized cysteine proteases activated in brain disorders. Likewise, during the last decade, extensive research revealed that the deregulation of calpains activity is a key cytotoxic event in a variety of neurodegenerative disorders. Moreover, interest in the role of calpain in neurodegenerative processes is growing due to implication of the involvement of cdk5 in neurodegenerative diseases. Since calpain inhibitors appear to not only protect brain tissue from ischemia, but also to prevent neurotoxicity caused by such neurotoxins as β‐amyloid or 3‐nitropropionic acid, the currently available data suggest that calpain and cdk5 play a key role in neuronal cell death. It seems clear that the inappropriate activation of cysteine proteases occurs not only during neuronal cell death, but may also contribute to brain pathology in ischemia and traumatic brain disorders. Pharmacological modulation of calpain activation may, therefore, be useful in the treatment of neurodegenerative disorders. It is possible, although difficult, to develop synthetic inhibitors of cysteine proteases, specifically calpains. The inhibition of calpain activation has recently emerged as a potential therapeutic target for the treatment of neurodegenerative diseases.