The Role of Calpain in Neurofilament Protein Degradation Associated With Spinal Cord Injury
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Calpain is a calcium-activated neutral proteinase present in all mammalian tissues thus far studied (1
,2
). Ubiquitous calpain exists as μ-calpain and m-calpain isoforms which require μM
and mM
calcium levels for activation, respectively. In the central nervous system (CNS) μ-calpain is predominantly cytosolic while
m-calpain is localized in both cytosolic and membrane fractions (2
). Although μ-calpain is largely neuronal and m-calpain is present predominantly in glial cells, both calpain isoforms share
similar substrate specificities and are inhibited by an endogenous inhibitor, calpastatin (2
). A broad range of proteins in the CNS, including cytoskeletal and myelin proteins such as neurofilament proteins (NFPs),
vimentin, micro-tubule-associated protein (MAP), and myelin basic protein (MBP) are known to be calpain substrates. The μ-and
m-calpains also cleave protein kinase C (PKC), hormones, receptors, and histones (3
).
