title: Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon.
abstract: Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases, and peripheral neuropathies. The calpain family of proteases has been mechanistically linked to the dysfunction and degeneration of axons. While the direct mechanisms by which transection, mechanical strain, ischemia, or complement activation trigger intra-axonal calpain activity are likely different, the downstream effects of unregulated calpain activity may be similar in seemingly disparate diseases. In this review, a brief examination of axonal structure is followed by a focused overview of the calpain family. Finally, the mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and specialized domains (axon initial segment, nodes, and terminals) are discussed.
authors: Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Resuscitation Science, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: marek_ma@yahoo.com.
authors: Marek
authors: M
authors: Ma
mesh_terms: D001369:Axons / Q000378:metabolism* / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology; D002154:Calpain / Q000502:physiology*; D006801:Humans; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D002154:Calpain
keywords: AAD; AIS; AMPA; Axon; CAM; CAP; CMAP; CNS; CSS1; CSS2; Calcium; Calpain; Caspr; Cav; DIC; DNA; DNase I; DRG; EDL; EGTA; GDC; GFP; HRP; IA; IP; IV; Ischemia; Kv; MAP; MCAO; NCX; NFH; NFL; NFM; NMJ; Na(+)–Ca(2+) exchanger; Nav; Neurofilament; Nmat-1; Node; NrCAM; OGD; PNS; Protease; SCG; SCI; Synapse; TAI; TBI; TTX; Trauma; UPS; Ube4b; Wallerian degeneration; YFP; ZNRF1; acute axonal degeneration; ankG; ankyrinG; axon initial segment; cell adhesion molecule; central nervous system; common small subunit 1; common small subunit 2; compound action potential; compound muscle action potential; contactin-associated protein; dSarm; deoxyribonuclease I; deoxyribonucleic acid; differential interference contrast; dorsal root ganglia; ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid; extensor digitorum longus; granular disintegration of the axonal cytoskeleton; green fluorescent protein; horseradish peroxidase; intra-arterial; intraperitoneal; intravenous; microtubule-associated protein; middle cerebral artery occlusion; neurofilament heavy; neurofilament light; neurofilament medium; neuromuscular junction; neuronal cell adhesion molecule; nicotinamide mononucleotide adenyl transferase 1; oxygen glucose deprivation; peripheral nervous system; spinal cord injury; sterile α/Armadillo/Toll–Interleukin receptor homology domain protein; sympathetic superior ganglia; tetrodotoxin; traumatic axonal injury; traumatic brain injury; ubiquitination factor E4B; ubiquitin–proteasome system; voltage-gated Ca(2+) channel; voltage-gated K(+) channel; voltage-gated Na(+) channel; yellow fluorescent protein; zinc and ring finger 1; α-amino-3-hydroxy-5-methylisoxazole-4-propionate; β-APP; β-amyloid precursor protein
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