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Calpain Family in Health and Diseases: The Road Ahead

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 2821

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Department of Biochemistry, Showa University School of Medicine, Tokyo 142-8555, Japan
Interests: protein–protein interactions; wound healing; aneurysmal diseases
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Dear Colleagues,

Calpains, Ca2+-dependent intracellular proteases, are comprised of 15 homologues in mammals, and are classified into conventional and unconventional isozymes. Conventional isozymes are composed of calpain-1 and -2, which are ubiquitously expressed in almost all eukaryotes. Growing evidence suggests that these conventional isozymes proteolytically modify intracellular signalling molecules, thereby altering cellular processes including inflammatory cascades. Accordingly, defective calpain-mediated proteolysis may be involved in the pathogenesis of human diseases, such as cardiometabolic disease, neurodegenerative disorders, and cancer progression. In contrast to the conventional isozymes, unconventional calpains are expressed in a tissue-specific manner. Earlier investigations have identified pathogenic roles of unconventional calpains in a variety of diseases, including cancer and retinal degeneration, whereas targeting calpain-3 can induce limb girdle muscular dystrophy type 2A (LGMD2A). The current Special Issue highlights the recent advances in molecular-based analyses of conventional and unconventional calpains to elucidate the pathophysiological aspects of these molecules and possible clinical applications.

Dr. Takuro Miyazaki
Guest Editor

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Keywords

  • chronic inflammation
  • gene-targeted mice
  • limited proteolytic cleavage
  • protein catabolism
  • cardiometabolic disease
  • cancer
  • neurodegenerative disease
 

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Published Papers (1 paper)

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Review

20 pages, 3351 KiB  
Review
Calpain and Cardiometabolic Diseases
by Takuro Miyazaki
Int. J. Mol. Sci. 2023, 24(23), 16782; https://doi.org/10.3390/ijms242316782 - 26 Nov 2023
Cited by 2 | Viewed by 2391
Abstract
Calpain is defined as a member of the superfamily of cysteine proteases possessing the CysPC motif within the gene. Calpain-1 and -2, which are categorized as conventional isozymes, execute limited proteolysis in a calcium-dependent fashion. Accordingly, the calpain system participates in physiological and [...] Read more.
Calpain is defined as a member of the superfamily of cysteine proteases possessing the CysPC motif within the gene. Calpain-1 and -2, which are categorized as conventional isozymes, execute limited proteolysis in a calcium-dependent fashion. Accordingly, the calpain system participates in physiological and pathological phenomena, including cell migration, apoptosis, and synaptic plasticity. Recent investigations have unveiled the contributions of both conventional and unconventional calpains to the pathogenesis of cardiometabolic disorders. In the context of atherosclerosis, overactivation of conventional calpain attenuates the barrier function of vascular endothelial cells and decreases the immunosuppressive effects attributed to lymphatic endothelial cells. In addition, calpain-6 induces aberrant mRNA splicing in macrophages, conferring atheroprone properties. In terms of diabetes, polymorphisms of the calpain-10 gene can modify insulin secretion and glucose disposal. Moreover, conventional calpain reportedly participates in amino acid production from vascular endothelial cells to induce alteration of amino acid composition in the liver microenvironment, thereby facilitating steatohepatitis. Such multifaceted functionality of calpain underscores its potential as a promising candidate for pharmaceutical targets for the treatment of cardiometabolic diseases. Consequently, the present review highlights the pivotal role of calpains in the complications of cardiometabolic diseases and embarks upon a characterization of calpains as molecular targets. Full article
(This article belongs to the Special Issue Calpain Family in Health and Diseases: The Road Ahead)
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