Calpain in the CNS: From Synaptic Function to Neurotoxicity
Jing Liu1*,
Ming Cheng Liu2,3, and
Kevin K. W. Wang1,2,3*
1Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute, Post Office Box 100256, University of Florida, Gainesville, FL 32610, USA.
2Center for Traumatic Brain Injury Studies, Department of Neuroscience, McKnight Brain Institute, Post Office Box 100256, University of Florida, Gainesville, FL 32610, USA.
3Center of Innovative Research, Banyan Biomarkers, Inc., 12085 Research Drive, Alachua, FL 32615, USA.
Abstract:
The calpains are a class of cellular cysteine proteases that require calcium and are functionally active at neutral pH. Calpain activation can take place in two modes: controlled activation under physiological conditions (in which only a few molecules of calpain are activated per cell), and hyperactivation under pathological conditions that involve sustained calcium overload (in which all available calpain molecules are activated). Regulated activation of calpain in the central nervous system (CNS) may be critical to synaptic function and memory formation, with possible substrates including various structural and scaffolding proteins, enzymes, and glutamate receptors. Hyperactivation of calpain in the central nervous system is generally associated with severe cellular challenge or damage. Calpain cleavage products may thus provide useful biomarkers for the presence of neurodegenerative processes or neuronal injury.
*Corresponding authors. E-mail: jingl{at}ufl.edu; kwang{at}banyanbio.com
