1993
DOI: 10.1073/pnas.90.7.2628
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Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration.

Abstract: Calcium-activated neutral proteinases (CANPs or calpains) are believed to be key enzymes in intracellular signaling cascades and potential mediators of calciuminduced neuronal degeneration. To investigate their involvement in Alzheimer disease, we identified three isoforms of ,uCANP (calpain I) in human postmortem brain corresponding to an 80-kDa precursor and two autolyticafly activated isoforms (78 and 76 kDa). As an index of changes in the in vivo activity of ,uCANP in Alzheimer disease, the ratio of the 76… Show more

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Cited by 546 publications
(401 citation statements)
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“…However, these studies showed different modes of calpain activation depending on the cell types and degenerative regions. Moreover, as for the degree of the calpain activation, normal aged human brain did not show activated calpain as much as Alzheimer's diseased brain (Saito et al, 1993;Tsuji et al, 1998). From these, we concluded that the lack of cleavage of fodrin and p35 processing in aged cortex of SD rats might be due to the differences in strains and/or species as mentioned by Kimura et al and less extent of normal aging than that of degenerative disorders.…”
Section: Discussionmentioning
confidence: 49%
“…However, these studies showed different modes of calpain activation depending on the cell types and degenerative regions. Moreover, as for the degree of the calpain activation, normal aged human brain did not show activated calpain as much as Alzheimer's diseased brain (Saito et al, 1993;Tsuji et al, 1998). From these, we concluded that the lack of cleavage of fodrin and p35 processing in aged cortex of SD rats might be due to the differences in strains and/or species as mentioned by Kimura et al and less extent of normal aging than that of degenerative disorders.…”
Section: Discussionmentioning
confidence: 49%
“…An increase in the intracellular free Ca +2 concentration triggers the calpain activation that cleaves many cytoskeletal and myelin proteins, which eventually results in apoptosis 2,17,28,51 . The overactivation of calpain is involved in the pathophysiology of neurodegenerative disorders and diseases and increases the lesion size as time passes after SCI 5,27,37,38,48 . After a primary injury to the spinal cord, the process of secondary injury progresses over time in the both rostral and caudal areas; this increases the lesion size and the rate Research has revealed that an SCI evokes an increase in the intracellular free Ca +2 level, which in turn results in the activation of calpain 17,51 .…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand calpain activity could be also negatively regulated by phosphorylation through PKA or its endogenous inhibitor calpastatin (Melloni et al, 1984;Inomata et al, 1988;Saido et al, 1992;Croall and McGrody, 1994;Moldoveanu et al, 2001;Shiraha et al, 2002;Dedieu et al, 2003(a)). The calpain family is thought to be involved in a range of various diseases such as cataract formation, diabetes, rheumatoid arthritis, ischemia, neurodegenerative diseases and muscular dystrophies (David et al, 1993;Saito et al, 1993;Mouatt-Prigent et al, 1996;Hirsch et al, 1997;Ishikawa et al, 1999;Horikawa et al, 2000;Richard et al, 2000;Tidball and Spencer 2000;Tamada et al, 2001;Trumbeckaite et al, 2003). Moreover, calpains play pivotal roles in physiological and biological phenomena such as signal transduction, cell spreading and motility, apoptosis, regulation of cell cycle, and regulation of muscle cell differentiation (Huttenlocher et al, 1997;Potter et al, 1998;Villa et al, 1998;Atencio et al, 2000;Barnoy et al, 2000;Cottin et al, 2000;Patel and Lane, 2000;Dourdin et al, 2001;Glading et al, 2001;Sato and Kawashima, 2001).…”
Section: Introductionmentioning
confidence: 99%