Novel inhibitors of the high-affinity l-proline transporter as potential therapeutic agents for the treatment of cognitive disorders

2014 ◽  
Vol 24 (16) ◽  
pp. 3886-3890 ◽  
Author(s):  
G. Greg Zipp ◽  
Joseph Barbosa ◽  
Michael A. Green ◽  
Kristen M. Terranova ◽  
Cynthia Fink ◽  
...  
2007 ◽  
Vol 123 ◽  
pp. S7
Author(s):  
Rebecca Ashfield ◽  
Deborah Sutton ◽  
Giovanna Bossi ◽  
Joanna Brewer ◽  
Marco Purbhoo ◽  
...  

2014 ◽  
Vol 68 (8) ◽  
Author(s):  
Eduardo Melo ◽  
Sidnei Moura e Silva ◽  
Fávero Paula

AbstractAnatoxin-a and epibatidine are natural toxins with a high affinity to nicotinic acetylcholine receptors (nAChR). Nicotinic ligands have the potential to become novel therapeutic agents for various cognitive disorders such as Alzheimer’s and Parkinson’s diseases. The determination of the physicochemical and biological properties of anatoxin-a and epibatidine derivatives is important because these might lead to the development of new cholinergic therapeutic agents. To study these features, the toxins and a set of their derivatives were subjected to a molecular modelling study and QSAR analysis. The structural analyses indicated that the geometric and steric features are important determinants of the compound’s activities. The descriptors selected for the QSAR model also highlighted the roles of the geometric and steric features, together with the importance of electronic features.


2021 ◽  
pp. 1-43
Author(s):  
Paula Silva ◽  
María Rodríguez-Pérez ◽  
Óscar Gómez-Torres ◽  
Emma Burgos-Ramos

Abstract Olive oil and wine are consumed daily worldwide and they constitute the fundamental pillars of the healthy Mediterranean diet. Polyphenolic compounds, naturally present in both olive oil and wine, are responsible for their beneficial properties. Current studies have shown the neuroprotective effects of polyphenols independently of their well-known antioxidant action. In this work, we have focused on reviewing the protective effect of polyphenols from extra virgin olive oil and wine in Alzheimer´s disease (AD), to emphasize that both food could be a possible therapeutic tool. Beneficial effects have been described in β-aggregation, neurofibrillary tangles, autophagy and mitochondrial function, as well as in cerebral insulin resistance. Furthermore, to date a harmful dose has not been described. Both preclinical and clinical works demonstrate that polyphenols act on neuropathological and cognitive disorders of AD, preventing or stopping the onset of this devastating disease. However, there are certain limitations in these studies, since it is very difficult to research diseases that lead to cognitive impairment. Although all the findings obtained are very encouraging, more studies should be carried out to use the polyphenols from olive oil and wine as therapeutic agents in the progression of AD. Therefore, more longitudinal studies in humans with a homogeneous cohort of patients are necessary to corroborate the efficacy of these nutraceuticals, as well as analyze which is the most appropriate dose for this purpose.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2243
Author(s):  
Fengling Feng ◽  
Jiaoshan Chen ◽  
Jin Zhao ◽  
Yanjun Li ◽  
Minchao Li ◽  
...  

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells mainly by the angiotensin converting enzyme 2 (ACE2) receptor, which can recognize the spike (S) protein by its extracellular domain. Previously, recombinant soluble ACE2 (sACE2) has been clinically used as a therapeutic treatment for cardiovascular diseases. Recent data demonstrated that sACE2 can also be exploited as a decoy to effectively inhibit the cell entry of SARS-CoV-2, through blocking SARS-CoV-2 binding to membrane-anchored ACE2. In this study, we summarized the current findings on the optimized sACE2-based strategies as a therapeutic agent, including Fc fusion to prolong the half-life of sACE2, deep mutagenesis to create high-affinity decoys for SARS-CoV-2, or designing the truncated functional fragments to enhance its safety, among others. Considering that COVID-19 patients are often accompanied by manifestations of cardiovascular complications, we think that administration of sACE2 in COVID-19 patients may be a promising therapeutic strategy to simultaneously treat both cardiovascular diseases and SARS-CoV-2 infection. This review would provide insights for the development of novel therapeutic agents against the COVID-19 pandemic.


Immunotherapy ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 19-33
Author(s):  
Eric Lespessailles ◽  
Hechmi Toumi

Psoriatic arthritis (PsA) is a heterogeneous chronic rheumatic disorder with numerous phenotypic facets. A better in deep understanding of the pathophysiologic mechanisms leading to psoriasis and PsA has contributed to the introduction of novel therapeutic agents. IL-17 is at the heart and a critical factor in the onset of PsA. Ixekizumab, a high-affinity monoclonal antibody against IL-17 A, has been approved by the US FDA in March 2016 for baseline psoriasis and Dec 2017 for PsA; by the EMA in April 2016 and January 2018, respectively. This article reviews the published data relating to ixekizumab efficacy and safety in the PsA treatment.


Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 941 ◽  
Author(s):  
Yang Zhang ◽  
Bo Lai ◽  
Mario Juhas

Aptamers are short, single-stranded DNA, RNA, or synthetic XNA molecules that can be developed with high affinity and specificity to interact with any desired targets. They have been widely used in facilitating discoveries in basic research, ensuring food safety and monitoring the environment. Furthermore, aptamers play promising roles as clinical diagnostics and therapeutic agents. This review provides update on the recent advances in this rapidly progressing field of research with particular emphasis on generation of aptamers and their applications in biosensing, biotechnology and medicine. The limitations and future directions of aptamers in target specific delivery and real-time detection are also discussed.


2018 ◽  
Vol 18 (1) ◽  
pp. 74-86 ◽  
Author(s):  
Ning Zhao ◽  
Yeshan Qin ◽  
Hongguang Liu ◽  
Zhen Cheng

The aberrant proliferation of tumor cells and abundant vasculature in tumor tissues are closely correlated with receptors that are specifically dysregulated in tumor cells. These tumor-associated targets are critical in early diagnosis and therapy selection. Ligands such as antibodies, proteins, polypeptides and polysaccharides that specifically bind to these targets can significantly improve the detection and cure rate when used as tumor imaging probes or anti-tumor agents. Compared to other targeting ligands, peptides have attracted increasingly more attention in tumor diagnostics and therapeutics because of their small sizes, high affinity, stability, ease of modification and low immunogenicity. Several peptide-based imaging probes and therapeutic agents have already been used in clinical trials. This review summarizes some of the tumor-associated targets and their corresponding peptides, as well as the potential of these peptides in cancer treatment.


2020 ◽  
Vol 21 (10) ◽  
pp. 810-817
Author(s):  
Yao Yu ◽  
Shiyuan Wang ◽  
Yakun Wang ◽  
Yiyin Cao ◽  
Chunlu Yu ◽  
...  

Background: Because of the high affinity of these animal neurotoxin proteins for some special target site, they were usually used as pharmacological tools and therapeutic agents in medicine to gain deep insights into the function of the nervous system. Background and Objective: The animal neurotoxin proteins are one of the most common functional groups among the animal toxin proteins. Thus, it was very important to characterize and predict the animal neurotoxin proteins. Methods: In this study, the differences between the animal neurotoxin proteins and non-toxin proteins were analyzed. Results: Significant differences were found between them. In addition, the support vector machine was proposed to predict the animal neurotoxin proteins. The predictive results of our classifier achieved the overall accuracy of 96.46%. Furthermore, the random forest and k-nearest neighbors were applied to predict the animal neurotoxin proteins. Conclusion: The compared results indicated that the predictive performances of our classifier were better than other two algorithms.


Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4267
Author(s):  
Valeriana Cesarini ◽  
Chiara Scopa ◽  
Domenico Alessandro Silvestris ◽  
Andrea Scafidi ◽  
Valerio Petrera ◽  
...  

Glioblastoma (GBM) is the most aggressive, infiltrative, and lethal brain tumor in humans. Despite the extensive advancement in the knowledge about tumor progression and treatment over the last few years, the prognosis of GBM is still very poor due to the difficulty of targeting drugs or anticancer molecules to GBM cells. The major challenge in improving GBM treatment implicates the development of a targeted drug delivery system, capable of crossing the blood–brain barrier (BBB) and specifically targeting GBM cells. Aptamers possess many characteristics that make them ideal novel therapeutic agents for the treatment of GBM. They are short single-stranded nucleic acids (RNA or ssDNA) able to bind to a molecular target with high affinity and specificity. Several GBM-targeting aptamers have been developed for imaging, tumor cell isolation from biopsies, and drug/anticancer molecule delivery to the tumor cells. Due to their properties (low immunogenicity, long stability, and toxicity), a large number of aptamers have been selected against GBM biomarkers and tested in GBM cell lines, while only a few of them have also been tested in in vivo models of GBM. Herein, we specifically focus on aptamers tested in GBM in vivo models that can be considered as new diagnostic and/or therapeutic tools for GBM patients’ treatment.


Sign in / Sign up

Export Citation Format

Share Document