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Collodion baby and harlequin ichthyosis
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
D. V. Lakshmi, Sahana M. Srinivas
The pathogenesis of the disease is attributed to structural and functional default of keratin, filaggrin, and the lamellar body. These are the main elements of the stratum corneum. Abnormal localization of epidermal lipids, abnormalities of keratinocyte nuclei, and distorted ultrastructure of lamellar granules lead to hyperkeratosis with hypergranulosis and parakeratosis of the epidermis, suggesting that the process of terminal differentiation is incomplete [22]. Alterations in protein phosphatase activity and calcium-mediated signaling are also implicated [23,24]. The causative genes were filaggrin, claudins, PP2A, and calpain 1 for the array of cellular phenotypes in HI. Also, in another study, the occurrence of serine-threonine protein phosphatase enzyme deficiency related to protein phosphatase gene mutations localized on the 11th chromosome were noted as another possible cause of this disease [24].
Micronutrients for the Prevention and Improvement of the Standard Therapy for Parkinson’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Downregulation of the expression of miR-124 was reduced the levels of its target protein Bim, a proapoptotic protein of Bcl2 family, and induced neurodegeneration in the MPTP mouse model of PD.94 The treatment with miR-124 agomir (a synthetic miR-124) protected DA neurons against MPTP-induced toxicity by decreasing the level of Bim. Another protein target for miR-124 was calpain 1, a calcium-dependent non-lysosomal cysteine proteases. MPTP treatment caused death of dopaminergic neurons by decreasing the expression of miR-124 and increasing the levels of calpain1.95 Overexpression of miR-124 decreased the levels of calpain1 and improved the survival of neurons. Silencing miR-124 increased production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2). The results suggest that one microRNA targets more than one mRNAs.
Effects of 6-(Methylsulfinyl)hexyl Isothiocyanate Ingestion on Muscle Damage after Eccentric Exercise in Healthy Males: A Pilot Placebo-Controlled Double-Blind Crossover Study
Published in Journal of Dietary Supplements, 2022
Yoko Tanabe, Nobuhiko Akazawa, Mio Nishimaki, Kazuhiro Shimizu, Naoto Fujii, Hideyuki Takahashi
The present study has several limitations. First, our study rationale regarding the effect of 6-MSITC on calpain levels relies on results provided in a patent application only (18). To the best of our knowledge, there is no peer-reviewed published research article that assessed this effect. Second, our sample size of eight might be insufficient to detect significant differences. Third, we assessed calpain-1 levels from blood samples. Given that calpain-1 is ubiquitously expressed throughout the body, the measured calpain-1 levels in this study might not purely reflect that in skeletal muscles. Fourth, we did not assess calpastatin, an endogenous selective inhibitor of calpain, which is involved in the regulation of calpain activity (41). Had we assessed calpastatin, we could have been able to delineate how 6-MSITC influenced the regulation of calpain activity. Fifth, the diet during the experiment was not strictly controlled, which might have influenced our results. Sixth, we did not assess the acute effect of 6-MSITC (e.g. after <24 h). Despite several limitations, it is noteworthy highlighting that the present study was well conducted with appropriate methods and design (e.g. a randomized, double-blind, crossover design). Therefore, data obtained in the present study is highly reliable and valuable.
Calpain as a therapeutic target in cancer
Published in Expert Opinion on Therapeutic Targets, 2022
Ivan Shapovalov, Danielle Harper, Peter A. Greer
The conventional calpain isoforms, calpain-1 and −2 (previously known as µ-calpain and m-calpain) were the first to be discovered and are the most well studied due to their abundant ubiquitous expression. Both isoforms are intracellular heterodimers consisting of a common regulatory subunit, encoded by the CAPNS1 gene (also known as CAPN4), and an isoform-specific catalytic subunit encoded by the CAPN1 or CAPN2 genes, for calpain-1 and calpain-2, respectively [10,11]. Calpain-1 and −2 are also considered classical calpains due to their defining domain structures. The catalytic subunit consists of an N-terminal anchor helix, a potential regulator of calpain activation [12]; two protease core domains that constitute the active site (PC1 and PC2); the calpain-type beta-sandwich (CBSW) domain (previously known as a C2-like domain); and a Ca2+ binding C-terminal penta EF-hand PEF(L) domain, a mediator of dimerization and a distinguishing feature of the classical calpain isoforms. The regulatory subunit CAPNS1 consists of an unstructured glycine rich (GR) domain; and a PEF(S) domain, which is homologous to the PEF(L) domain. A crystal structure of calpain-2 and domain maps for the catalytic (CAPN1/2) and regulatory (CAPNS1) subunits are shown in Figure 1.
Calpain-2 as a therapeutic target for acute neuronal injury
Published in Expert Opinion on Therapeutic Targets, 2018
Yubin Wang, Xiaoning Bi, Michel Baudry
Of the 15 isoforms, calpain-1 and calpain-2 are ubiquitously expressed, predominantly in mammalian brain and have been the most extensively studied. Calpain-1 and calpain-2 are generally soluble and are present in both neurons and glia. For activity, calpain-1 or calpain-2 require their association with a small regulatory subunit (calpain-S1, formerly known as calpain-4) to form functional heterodimeric proteins. The large catalytic subunit for calpain-1 or calpain-2 contains four major domains. Domain I is the N-terminal anchor helix region of the large subunit, which can undergo autolysis following calpain activation by Ca2+ [23]. Domain II comprises two protease core domains (PC1 and PC2), which fuse to form the active cysteine catalytic region upon Ca2+ binding onto each core domain [24]. Domain III is involved in binding Ca2+ and phospholipids [25]. Domain IV exhibits a penta-EF-hand calcium-binding domain and contributes to the heterodimer formation [26].