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Paragonimus
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Pham Ngoc Doanh, Haruhiko Maruyama, David Blair, Yukifumi Nawa
Throughout this migration, intense inflammation is elicited around the invading worms by secreted digestive enzymes, namely, cathepsin F cysteine proteases.58 Destruction of cells and tissues with enzymes induces natural lymphocytes secreting type 2 cytokines, resulting in type 2–dominated acquired immunity.59,60 Therefore, potent peripheral blood eosinophilia and IgE responses are elicited, which are major clues to the diagnosis of paragonimiasis.
A patent review on cathepsin K inhibitors to treat osteoporosis (2011 – 2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Fernanda R. Rocho, Vinícius Bonatto, Rafael F. Lameiro, Jerônimo Lameira, Andrei Leitão, Carlos A. Montanari
Stachel et al. from Merck & Co. (USA) published two patents using the same class of nitrile compounds. In one of the patents [57], a library of 159 compounds was studied, and immunoprecipitation (IP) values were specified for CatK and Cathepsin F (CatF). The best inhibitor presented was compound 2, with an IP value of 0.28 nM for CatK and 71 nM for CatF. In the second patent [58], the authors claimed 248 nitrile compounds, which were structurally similar to the first one [57]. Values of IP were also provided for CatK and CatF, with compound 3 presenting IP values of 0.3 nM for CatK and 35 nM for CatF. Interestingly, the only structural change between compounds 2 and 3 is the replacement of an oxazole for a thiazole. The changes between the compounds demonstrate that the groups are equivalent regarding CatK, but not against CatF, once compound 3 performed better. In both patents, the authors mentioned kinetic assays against cathepsins K, L, S, B, and F and in vivo experiments using male Sprague Dawley rat line, but no results were displayed (Figure 4).
Advances in the treatment of neuronal ceroid lipofuscinosis
Published in Expert Opinion on Orphan Drugs, 2019
Jonathan B. Rosenberg, Alvin Chen, Stephen M. Kaminsky, Ronald G. Crystal, Dolan Sondhi
CLN13 disease, also known as Kufs disease type B, is characterized by adult onset dementia, often associated with movement and behavioral abnormalities [90,91]. The disease is caused by mutations in the gene encoding cathepsin-F, a lysosomal cysteine protease [90,91]. Symptoms usually present around 30 years of age, starting with memory deficits and behavioral disturbances. As the disease progresses, motor function deteriorates and brain function decreases. Affected individuals develop tremors, bradykinesia, and extrapyramidal type rigidity. CLN13 is rare among the NCL family of diseases, and unlike most NCLs there is no loss of vision [90,91].
New discoveries in progressive myoclonus epilepsies: a clinical outlook
Published in Expert Review of Neurotherapeutics, 2018
Shweta Bhat, Subramaniam Ganesh
Broadly, almost all the gene products or proteins identified to be defective in NCLs can be grouped under one broad functional category: that they are involved in cellular homeostatic processes, involving proteolysis (autophagy, lysosome, and proteasomal degradation) and lipid metabolism. Two of the proteins are vesicular membrane proteins (CLN-4 and CLN-14), and the other localizing on the endosomal (CLN-6 and CLN-8) or lysosomal compartments (CLN-1, CLN-2, CLN-3, CLN-5, CLN-7, CLN-10, CLN-12, and CLN-13). Proteins encoded by CLN-10 and CLN-13 are lysosomal soluble proteins. Despite the progress made in identifying and characterizing the genes involved in NCLs, the precise mechanism underlying the individual NCL phenotype is still unknown. What is known is that the deficiency of any of the functional protein invariably leads to accumulation of ceroid-lipopigments, subunit c of mitochondrial ATP synthase or sphingolipid activator proteins A and D in lysosomes leading to neurodegeneration and associated CNS aberrations. Palmitoyl-protein thioesterase 1 (PPT1) coded by CLN-1, the Tripeptidyl-peptidase 1 (TPP1) coded by CLN-2, a transmembrane protein coded by CLN-3, Cysteine-string protein alpha (CSPα)/DNAJC5 coded by CLN-4 are demonstrated to be involved in synaptic endo or exocytosis, normal neurotransmission, and apoptosis. Apart from this general involvement, individual, protein-specific functions are also reported. For example, Cathepsin D (Aspartyl endopeptidase) and Cathepsin F (Cysteine protease) encoded by CLN-10 and CLN-13 are thought to play a role in apoptosis, autophagy, and proteasomal and lipoprotein degradation, respectively. A detailed description of cellular functions of these proteins can be found elsewhere [63,66], and summary is provided in Table 2.