REVIEW: Pleiotropic Functions of Brain Proteinases: Methodological Considerations and Search for Caspase Substrates

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A. A. Yakovlev and N. V. Gulyaeva^*

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, ul. Butlerova 5a, 117485 Moscow, Russia; fax: (495) 952-4007; E-mail: nata_gul@pisem.net; nata_gul@yahoo.com

^* To whom correspondence should be addressed.

Received March 16, 2011; Revision received April 17, 2011

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Analysis of the literature and our own data suggest that the so-called “apoptotic” proteinases play important roles in brain function. However, mechanisms of their involvement in normal neuronal plasticity remain obscure. One of the main reasons for this is broad substrate specificity of proteinases; the number of potential substrates of each can reach several thousands. Obviously, a real approach to study functions of “apoptotic” proteinases, caspase-3 in particular, is to identify their intracellular substrates. It is the nature of a substrate that defines the direction of signal transduction or metabolic changes; therefore, identification of molecular partners of particular proteases should be the key study, not just measuring its activity or respective protein or mRNA expression. This approach will allow studying regulatory mechanisms not only for proteinases, but also for other pleiotropic enzymes usually possessing broad substrate specificity.

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KEY WORDS: proteinases, caspase, proteinase substrates, broad substrate specificity, plasticity, apoptosis, brain

DOI: 10.1134/S0006297911100014

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