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Chronic Otitis Media
Published in John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed, Paediatrics, The Ear, Skull Base, 2018
George G. Browning, Justin Weir, Gerard Kelly, Iain R.C. Swan
Genome-wide linkage studies have identified OM susceptibility loci at several regions of linkage on chromosomes 3p25, 10q22, 10q26, 17q12 and 19q13.35,39,40 To date, the susceptibility genes underlying these linkage regions have not been mapped, though Casselbrant et al. 39 proposed a cluster of chemokine genes on 17q12 and several surfactant protein genes near 10q26, while Daly et al. 35 proposed ADAM8 gene (a disintegrin and metalloproteinase domain), an allergy-associated gene, as a possible candidate for 10q22 linkage peak and Chen et al. 40 suggested potential candidate genes at 19q such as ZNF71, an endothelial zinc finger gene induced by TNF-±, and ZNF304, which activates lymphocytes.41 Other candidate genes included members of the inflammasome protein complex which are key regulators of the innate immune response to harmful exogenous or endogenous stimuli.
Transmembrane protein ADAM29 facilitates cell proliferation, invasion and migration in clear cell renal cell carcinoma
Published in Journal of Chemotherapy, 2020
Shun-Lai Li, Ting-Qi Jiang, Qing-Wei Cao, Shan-Mei Liu
A disintegrin and metalloprotease (ADAM) family, also known as metalloproteinolytic depolymerization, is a type І transmembrane protein.9 It has a zinc binding domain similar to that of matrix metalloproteinases (MMPs) and a functional binding domain similar to that of the metalloprotease-disintegrin-cysteinerich (MDC) family, which plays a role in proteolytic processing of cell surface molecules and in cell adhesion.10,11 The involvement of ADAMs in regulation of cell-cell adhesion and cell-matrix interactions suggests that they not only play a potential effect in normal physiological processes, but also provide a basis for considering the participation in tumour biology and their ability to invade and metastasize.12 Previous reports have demonstrated that multiple members of ADAM family, including ADAM29, are abnormally expressed in a variety of cancers, which may be closely connected with the development of tumours.13–16 Currently, in RCC, several ADAMs (8, 9, 17, 19, and 28) have already been shown upregulated on transcript level, with ADAM8 and ADAM9 being correlated with poor survival and distant metastasis.17,18 But, the role of ADAM29 in ccRCC remains unclear.
Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part II: strategies for therapeutics development
Published in Expert Review of Neurotherapeutics, 2021
The selection of an optimal α-secretase ADAM for augmentation will be both a challenging task and a critical factor for outcomes. Of the known ADAMs implicated in PrP processing, ADAM10 was initially reported to contribute to the α-cleavage of PrPC [29,31,35,71], and it seems to be an attractive candidate to be enhanced for a number of reasons described below. But the PrPC α-cleavage activity of ADAM10 is strongly disputed and appears to be ruled out by later experiments with neuron-specific conditional ADAM10-knockout or ADAM10-overexpressing mice or cells [30,32,54]. Nevertheless, ADAM10 remains an interesting protein for therapeutic purposes even if it is not involved in PrPC α-cleavage. One of the reasons is that ADAM10 is the primary PrP sheddase [56] that produces an extracellular PrP form (termed shed PrP) with protective activities [38,45–48], and it plays a key role in the non-amyloidogenic α-cleavage of APP [72,73], making it a notable target for AD therapy development [72–74]. Transgenic mice overexpressing ADAM10 in neurons showed increased neurotrophic N-terminal APP domain (APPsα), reduced soluble Aβ peptides, diminished Aβ plaques, and partially rescued LTP [74]. Additionally, the increased levels of ADAM10 did not seem to cause significant detrimental phenotypic alterations [29,54,74,75], suggesting that enhancing APP α-cleavage activities through augmenting ADAM10 is a viable strategy. It is worth noting that high-level neuronal overexpression of ADAM10 was reported to cause more seizures and stronger neuronal damage and inflammation after kainate-induced epileptic seizures [76]. In addition, ADAM10 is known to promote cancer [77] and it is a target for cancer and autoimmunity therapies [78], suggesting that enhancement of ADAM10 activity needs to be done carefully and kept at moderate levels. Moreover, transgenic neuronal overexpression of ADAM10 in mice led to a decrease in total PrP levels rather than an increase of specific PrPC cleavage products as well as enhanced survival of the mice when challenged with prions [54]. If the same is true when the ADAM10 activity is elevated through administration of recombinant ADAM10 or expression from a gene therapy vector, augmenting ADAM10 should still protect against AD, PD, and other neurodegenerative diseases through decreasing cell surface PrPC levels. Whether ADAM8 and/or the yet-to-be identified other PrPC α-cleavage enzyme(s) can be targeted to fight AD and other neurodegenerative diseases awaits further studies.