Bromelain: A potential therapeutic application in SARS-CoV-2 infected patients

AbstractProgranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative diseases is huge. Thus, strategies to increase PGRN levels in patients could provide an effective treatment. In the present study, we investigated the effects of AZP2006, a lysotropic molecule now in phase 2a clinical trial in Progressive Supranuclear Palsy patients, for its ability to increase PGRN level and promote neuroprotection. We showed for the first time the in vitro and in vivo neuroprotective effects of AZP2006 in neurons injured with Aβ1–42 and in two different pathological animal models of Alzheimer’s disease (AD) and aging. Thus, the chronic treatment with AZP2006 was shown to reduce the loss of central synapses and neurons but also to dramatically decrease the massive neuroinflammation associated with the animal pathology. A deeper investigation showed that the beneficial effects of AZP2006 were associated with PGRN production. Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases.

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A new immunomodulating compound (AS-101) with potential therapeutic application

Nature ◽

10.1038/330173a0 ◽

1987 ◽

Vol 330 (6144) ◽

pp. 173-176 ◽

Cited By ~ 123

Author(s):

B. Sredni ◽

R. R. Caspi ◽

A. Klein ◽

Y. Kalechman ◽

Y. Danziger ◽

...

Keyword(s):

Therapeutic Application ◽

Potential Therapeutic Application ◽

Immunomodulating Compound

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Kororamides, Convolutamines, and Indole Derivatives as Possible Tau and Dual-Specificity Kinase Inhibitors for Alzheimer’s Disease: A Computational Study

Marine Drugs ◽

10.3390/md16100386 ◽

2018 ◽

Vol 16 (10) ◽

pp. 386 ◽

Cited By ~ 10

Author(s):

Laura Llorach-Pares ◽

Alfons Nonell-Canals ◽

Conxita Avila ◽

Melchor Sanchez-Martinez

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Therapeutic Strategy ◽

Kinase Inhibitors ◽

Computational Study ◽

Therapeutic Application ◽

Ongoing Research ◽

Casein Kinase 1 ◽

Dual Specificity ◽

Potential Therapeutic Application

Alzheimer’s disease (AD) is becoming one of the most disturbing health and socioeconomic problems nowadays, as it is a neurodegenerative pathology with no treatment, which is expected to grow further due to population ageing. Actual treatments for AD produce only a modest amelioration of symptoms, although there is a constant ongoing research of new therapeutic strategies oriented to improve the amelioration of the symptoms, and even to completely cure the disease. A principal feature of AD is the presence of neurofibrillary tangles (NFT) induced by the aberrant phosphorylation of the microtubule-associated protein tau in the brains of affected individuals. Glycogen synthetase kinase-3 beta (GSK3β), casein kinase 1 delta (CK1δ), dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) and dual-specificity kinase cdc2-like kinase 1 (CLK1) have been identified as the principal proteins involved in this process. Due to this, the inhibition of these kinases has been proposed as a plausible therapeutic strategy to fight AD. In this study, we tested in silico the inhibitory activity of different marine natural compounds, as well as newly-designed molecules from some of them, over the mentioned protein kinases, finding some new possible inhibitors with potential therapeutic application.

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The physiology, pathology and potential therapeutic application of serotonylation

Journal of Cell Science ◽

10.1242/jcs.257337 ◽

2021 ◽

Vol 134 (11) ◽

Author(s):

Shu-Heng Jiang ◽

Ya-Hui Wang ◽

Li-Peng Hu ◽

Xu Wang ◽

Jun Li ◽

...

Keyword(s):

Matrix Protein ◽

Small Gtpases ◽

Cytoskeletal Proteins ◽

Extracellular Matrix Protein ◽

Post Translational Modification ◽

Pharmacological Interventions ◽

Therapeutic Application ◽

Disease Treatment ◽

Physiological Processes ◽

Potential Therapeutic Application

ABSTRACT The classical neurotransmitter serotonin or 5-hydroxytryptamine (5-HT), synthesized from tryptophan, can be produced both centrally and peripherally. Through binding to functionally distinct receptors, serotonin is profoundly implicated in a number of fundamental physiological processes and pathogenic conditions. Recently, serotonin has been found covalently incorporated into proteins, a newly identified post-translational modification termed serotonylation. Transglutaminases (TGMs), especially TGM2, are responsible for catalyzing the transamidation reaction by transferring serotonin to the glutamine residues of target proteins. Small GTPases, extracellular matrix protein fibronectin, cytoskeletal proteins and histones are the most reported substrates for serotonylation, and their functions are triggered by this post-translational modification. This Review highlights the roles of serotonylation in physiology and diseases and provides perspectives for pharmacological interventions to ameliorate serotonylation for disease treatment.

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