Cathepsin D—Managing the Delicate Balance

Mijanović, Olja; Petushkova, Anastasiia I.; Branković, Ana; Turk, Boris; Solovieva, Anna B.; Nikitkina, Angelina I.; Bolevich, Sergey; Timashev, P. S.; Parodi, Alessandro; Zamyatnin, Andrey A.

doi:10.3390/pharmaceutics13060837

Cited by 46 publications

(31 citation statements)

References 147 publications

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“…Tamoxifen. It increases the production of cathepsin D, which helps to prevent this disease from occurring since it has been shown that many neurodegenerative diseases arise when there are low levels of cathepsin D or it is inactive, causing failures in one of the genes that produces this disease [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

et al. 2022

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Rare diseases are a group of uncommon diseases in the world population. To date, about 7000 rare diseases have been documented. However, most of them do not have a known treatment. As a result of the relatively low demand for their treatments caused by their scarce prevalence, the pharmaceutical industry has not sufficiently encouraged the research to develop drugs to treat them. This work aims to analyse potential drug-repositioning strategies for this kind of disease. Drug repositioning seeks to find new uses for existing drugs. In this context, it seeks to discover if rare diseases could be treated with medicines previously indicated to heal other diseases. Our approaches tackle the problem by employing computational methods that calculate similarities between rare and non-rare diseases, considering biological features such as genes, proteins, and symptoms. Drug candidates for repositioning will be checked against clinical trials found in the scientific literature. In this study, 13 different rare diseases have been selected for which potential drugs could be repositioned. By verifying these drugs in the scientific literature, successful cases were found for 75% of the rare diseases studied. The genetic associations and phenotypical features of the rare diseases were examined. In addition, the verified drugs were classified according to the anatomical therapeutic chemical (ATC) code to highlight the types with a higher predisposition to be repositioned. These promising results open the door for further research in this field of study.

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Section: Resultsmentioning

confidence: 99%

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

et al. 2022

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“…The peptide mediated inhibition of BACE-2 and CTSD could also be a beneficial therapy since BACE-2 plays a significant role in enhanced neurodegeneration in Alzheimer's disease, tumor progression such as in glioma, melanoma etc. (Farris et al 2021) and CTSD is also involved in various neurodegenerative disorders and cancers such as melanoma, breast cancer, prostate cancer etc (Mijanovic et al 2021).…”

Section: Discussionmentioning

confidence: 99%

In silico design of bioactive chimeric peptide from archaeal antimicrobial peptides

Banerjee

Chakraborty

Majumder

2021

Preprint

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The adverse role of multi-drug resistant bacterial biofilms accelerating human chronic diseases has posed a great risk to present world. Devising a therapy to impede such perilous effects is the need of the moment. So, in this study, we have designed a novel peptide therapy involving archaeal antimicrobial peptides. In silico predictions assign the peptide construct to be antigenic, non-allergenic, anti-cancerous and having stable physicochemical properties. Computational tools predict intracellular receptors in Escherichia coli and human to be possible binding targets of the construct. In silico docking of modelled peptide with targets, validated the predicted estimations. Coincidentally few human receptors binding strongly to the peptide, tend to be the widely recognized targets associated to human diseases with severe complications. Studies of conformational dynamics of peptide docked complexes with human and bacterial targets, indicated stable binding of the modelled construct. Certainly, the designed peptide could be a potent therapeutic against biofilms and human disorders.

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“…Through its endopeptidase activity, CatD modulates the activity of diverse polypeptides, growth factors, and enzymes and the degradation of misfolded, long‐lived, and denatured proteins. Accordingly, CatD is considered an essential regulator of cell signaling and cellular homeostasis [ 31 ]. Dysregulated CatD activity plays an important role in diseases such as acute kidney injury, coronary events, neurodegenerative diseases, and cancer (reviewed in [ 31 , 32 , 33 , 34 ]).…”

Section: Lysosomal Peptidasesmentioning

confidence: 99%

“…Accordingly, CatD is considered an essential regulator of cell signaling and cellular homeostasis [ 31 ]. Dysregulated CatD activity plays an important role in diseases such as acute kidney injury, coronary events, neurodegenerative diseases, and cancer (reviewed in [ 31 , 32 , 33 , 34 ]).…”

Section: Lysosomal Peptidasesmentioning

confidence: 99%

Lysosomal peptidases—intriguing roles in cancer progression and neurodegeneration

et al. 2022

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Lysosomal peptidases are hydrolytic enzymes capable of digesting waste proteins that are targeted to lysosomes via endocytosis and autophagy. Besides intracellular protein catabolism, they play more specific roles in several other cellular processes and pathologies, either within lysosomes, upon secretion into the cell cytoplasm or extracellular space, or bound to the plasma membrane. In cancer, lysosomal peptidases are generally associated with disease progression, as they participate in crucial processes leading to changes in cell morphology, signaling, migration, and invasion, and finally metastasis. However, they can also enhance the mechanisms resulting in cancer regression, such as apoptosis of tumor cells or antitumor immune responses. Lysosomal peptidases have also been identified as hallmarks of aging and neurodegeneration, playing roles in oxidative stress, mitochondrial dysfunction, abnormal intercellular communication, dysregulated trafficking, and the deposition of protein aggregates in neuronal cells. Furthermore, deficiencies in lysosomal peptidases may result in other pathological states, such as lysosomal storage disease. The aim of this review was to highlight the role of lysosomal peptidases in particular pathological processes of cancer and neurodegeneration and to address the potential of lysosomal peptidases in diagnosing and treating patients.

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Cathepsin D—Managing the Delicate Balance

Cited by 46 publications

References 147 publications

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

In silico design of bioactive chimeric peptide from archaeal antimicrobial peptides

Lysosomal peptidases—intriguing roles in cancer progression and neurodegeneration

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