The Binary Classification of Protein Kinases

Elkoshi, Zeev

doi:10.2147/jir.s303750

Cited by 4 publications

(5 citation statements)

References 164 publications

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“…The protein kinase family is a very large group of kinases (in men more than 500) catalyzing the phosphorylation of proteins. Their role in the control of various cellular functions, involving proliferation, apoptosis, metabolism, and others is of great importance (Elkoshi 2021 ). Disturbed regulation of protein kinases is linked with the appearance of many cancers, such as breast, pancreatic, lung, and other cancers as well as autoimmune diseases such as rheumatoid arthritis and psoriasis.…”

Section: Ros-mediated Cell Signalingmentioning

confidence: 99%

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Jomova,

Raptova,

Alomar

et al. 2023

Arch Toxicol

300

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A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related factor 2 (Nrf2) and other processes. Increased levels of ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result in a harmful condition termed oxidative stress (“bad stress”). Although it is widely accepted, that many chronic diseases are multifactorial in origin, they share oxidative stress as a common denominator. Here we review the importance of oxidative stress and the mechanisms through which oxidative stress contributes to the pathological states of an organism. Attention is focused on the chemistry of ROS and RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, nitric oxide, peroxynitrite), and their role in oxidative damage of DNA, proteins, and membrane lipids. Quantitative and qualitative assessment of oxidative stress biomarkers is also discussed. Oxidative stress contributes to the pathology of cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s and Parkinson’s diseases, Down syndrome), psychiatric diseases (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, lung cancer), and aging. The concerted action of antioxidants to ameliorate the harmful effect of oxidative stress is achieved by antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), and small molecular weight antioxidants (vitamins C and E, flavonoids, carotenoids, melatonin, ergothioneine, and others). Perhaps one of the most effective low molecular weight antioxidants is vitamin E, the first line of defense against the peroxidation of lipids. A promising approach appears to be the use of certain antioxidants (e.g. flavonoids), showing weak prooxidant properties that may boost cellular antioxidant systems and thus act as preventive anticancer agents. Redox metal-based enzyme mimetic compounds as potential pharmaceutical interventions and sirtuins as promising therapeutic targets for age-related diseases and anti-aging strategies are discussed.

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Section: Ros-mediated Cell Signalingmentioning

confidence: 99%

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Jomova,

Raptova,

Alomar

et al. 2023

Arch Toxicol

300

View full text Add to dashboard Cite

show abstract

“…In scientific databases, such as the Protein Data Bank (PDB), protein structures and inhibitory complexes related to more than 300 kinases are available for drug design studies ( Laufer et al., 2020 ). The web computational resource (KinCore) predicts the dynamic states of PKs in association with inhibitors, contributing to the identification of more efficient kinase inhibitors ( Modi and Dunbrack, 2022 ) and opening new avenues for the application of safe chemotherapies against a variety of diseases ( Elkoshi, 2021 ). In addition, Uniprot ( www.uniprot.org ) provides more than 2,000 three-dimensional structures related to human PKs, which can contribute to developing specific kinase inhibitors for therapeutic applications against apicomplexan parasites.…”

Section: Protein Kinases: General Aspects Classification and Regulato...mentioning

confidence: 99%

Protein kinases on carbon metabolism: potential targets for alternative chemotherapies against toxoplasmosis

Santos

Souza

Silber

et al. 2023

Front. Cell. Infect. Microbiol.

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The apicomplexan parasite Toxoplasma gondii is the causative agent of toxoplasmosis, a global disease that significantly impacts human health. The clinical manifestations are mainly observed in immunocompromised patients, including ocular damage and neuronal alterations leading to psychiatric disorders. The congenital infection leads to miscarriage or severe alterations in the development of newborns. The conventional treatment is limited to the acute phase of illness, without effects in latent parasites; consequently, a cure is not available yet. Furthermore, considerable toxic effects and long-term therapy contribute to high treatment abandonment rates. The investigation of exclusive parasite pathways would provide new drug targets for more effective therapies, eliminating or reducing the side effects of conventional pharmacological approaches. Protein kinases (PKs) have emerged as promising targets for developing specific inhibitors with high selectivity and efficiency against diseases. Studies in T. gondii have indicated the presence of exclusive PKs without homologs in human cells, which could become important targets for developing new drugs. Knockout of specific kinases linked to energy metabolism have shown to impair the parasite development, reinforcing the essentiality of these enzymes in parasite metabolism. In addition, the specificities found in the PKs that regulate the energy metabolism in this parasite could bring new perspectives for safer and more efficient therapies for treating toxoplasmosis. Therefore, this review provides an overview of the limitations for reaching an efficient treatment and explores the role of PKs in regulating carbon metabolism in Toxoplasma, discussing their potential as targets for more applied and efficient pharmacological approaches.

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“…Indeed, the World Health Organization recommends the use of CS in severe COVID-19 but not in mild disease (see Discussion). B. JAK inhibitors: most JAK inhibitors induce an antiinflammatory effect expressed by increased Tregs activity and/ or decreased Th17 activity (18). The effect of JAK inhibitors on CTL may vary from drug to drug.…”

Section: A Corticosteroids: Corticosteroids (Cs) Have Shown To Promotementioning

confidence: 99%

The Binary Model of Chronic Diseases Applied to COVID-19

Elkoshi

2021

Front. Immunol.

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A binary model for the classification of chronic diseases has formerly been proposed. The model classifies chronic diseases as “high Treg” or “low Treg” diseases according to the extent of regulatory T cells (Treg) activity (frequency or function) observed. The present paper applies this model to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The model correctly predicts the efficacy or inefficacy of several immune-modulating drugs in the treatment of severe coronavirus disease 2019 (COVID-19) disease. It also correctly predicts the class of pathogens mostly associated with SARS-CoV-2 infection. The clinical implications are the following: (a) any search for new immune-modulating drugs for the treatment of COVID-19 should exclude candidates that do not induce “high Treg” immune reaction or those that do not spare CD8+ T cells; (b) immune-modulating drugs, which are effective against SARS-CoV-2, may not be effective against any variant of the virus that does not induce “low Treg” reaction; (c) any immune-modulating drug, which is effective in treating COVID-19, will also alleviate most coinfections; and (d) severe COVID-19 patients should avoid contact with carriers of “low Treg” pathogens.

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The Binary Classification of Protein Kinases

Cited by 4 publications

References 164 publications

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Protein kinases on carbon metabolism: potential targets for alternative chemotherapies against toxoplasmosis

The Binary Model of Chronic Diseases Applied to COVID-19

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