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

Nature ◽  
1987 ◽  
Vol 330 (6144) ◽  
pp. 173-176 ◽  
Author(s):  
B. Sredni ◽  
R. R. Caspi ◽  
A. Klein ◽  
Y. Kalechman ◽  
Y. Danziger ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
N. Callizot ◽  
C. Estrella ◽  
S. Burlet ◽  
A. Henriques ◽  
C. Brantis ◽  
...  

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.


Marine Drugs ◽  
2018 ◽  
Vol 16 (10) ◽  
pp. 386 ◽  
Author(s):  
Laura Llorach-Pares ◽  
Alfons Nonell-Canals ◽  
Conxita Avila ◽  
Melchor Sanchez-Martinez

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.


2021 ◽  
Vol 134 (11) ◽  
Author(s):  
Shu-Heng Jiang ◽  
Ya-Hui Wang ◽  
Li-Peng Hu ◽  
Xu Wang ◽  
Jun Li ◽  
...  

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.


2013 ◽  
Vol 75 (3) ◽  
pp. 349-354 ◽  
Author(s):  
Nobuyuki FUJIWARA ◽  
Hideyoshi KAWASAKI ◽  
Ryotaro YABE ◽  
Dale J. CHRISTENSEN ◽  
Michael P. VITEK ◽  
...  

Viruses ◽  
2015 ◽  
Vol 8 (1) ◽  
pp. 3 ◽  
Author(s):  
Diana Sánchez ◽  
Rosana Pelayo ◽  
Luis Medina ◽  
Eduardo Vadillo ◽  
Rogelio Sánchez ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Enrico Brunetta ◽  
Dana Shiffer ◽  
Marco Folci ◽  
Maria I. S. Achenza ◽  
Francesca Puggioni ◽  
...  

Presently, there is inconclusive evidence regarding the most effective treatment for idiopathic nonhistaminergic acquired angioedema (InH-AAE). Omalizumab may, however, prove to be a promising option. This case report describes two patients who presented with recurrent angioedema attacks, which was refractory to antihistamine therapy. Hence, they were treated with 300 mg omalizumab, every 4 weeks, for a period of 6 months. Both patients had shown a rapid response to the treatment and achieved complete resolution of symptoms without further AE attacks throughout the entire duration of the treatment period. After omalizumab’s suspension, one patient remained symptom free for the following 6 months and the other patient had recurrence of symptoms after 2 months for which he was retreated with omalizumab and once again became symptom free. Although omalizumab seems to be effective as a prophylactic treatment for InH-AAE, the determining factors leading to the differences in time-to-relapse between patients after its suspension remain unclear. Further studies are needed in order to better determine the potential therapeutic application of omalizumab and its role in maintenance therapy.


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