Current Drug Targets - Volume 23, Issue 11, 2022

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment and cognitive decline. The obvious pathological features of AD are still amyloid plaques and neurofibrillary tangles. Development of disease-modifying treatments for AD has been challenging, with almost all drugs aborted. The amyloid cascade concept has been questioned due to the failures of various amyloid-targeting prospects. Despite this, targeting amyloid-β (Aβ) active immunotherapy provided some positive results to support this hypothesis and clinical trials of these candidates are ongoing. In this review, we describe the latest advance in therapeutic strategies based on amyloidogenic processing and evaluate the pros and cons of each treatment strategy. We also highlight the current status of the hottest immunotherapy and discuss the future development direction.

Obesity and type 2 diabetes mellitus (T2DM), as common metabolic diseases, are pathologically characterized by overnutrition and insulin resistance (IR), which subsequently lead to glucose and lipid metabolism disorders. The liver, a major metabolic organ of the body, integrates hormone and metabolic signals to regulate the synthesis of lipids and glucose as well as their transport to peripheral tissues, hence playing an essential role in the development of obesity and T2DM. Adenosine 5’-monophosphate-activated protein kinase (AMPK) is a central regulator involved in cellular and organismal metabolism in eukaryotes, which activates processes that produce ATP and diminishes its consumption. In addition, AMPK also regulates mitochondrial homeostasis and promotes autophagy, both of which are associated with the pathogenesis of IR. Therefore, increasing AMPK activity is considered a promising therapeutic strategy to prevent obesity and T2DM. In this review, we summarize the role of hepatic AMPK in obesity and T2DM and the potential of using AMPK activators as therapeutics for metabolic disorders.

The efficacy of the cancer vaccine is influenced by several factors, but one of the most important is the immunosuppressive tumor microenvironment, which can attenuate treatment effects. The combination of therapeutic cancer vaccines with other immunotherapies or conventional therapeutic approaches can promote vaccine efficacy by increasing immune surveillance and tumor immunogenicity and modulating immune escape in the tumor microenvironment. Inhibitory checkpoints have a significant role in the modulation of anticancer immune responses, and according to preclinical and clinical trials, administration of immune checkpoint inhibitors (ICIs) in combination with cancer vaccines can markedly improve their therapeutic effects, considering their low clinical efficacy. In addition, these combinatorial therapies have acceptable safety and minimal additional toxicity compared to single-agent cancer vaccines or ICIs. In this review, based on the results of previous studies, we introduce and discuss treatments that can be combined with therapeutic cancer vaccines to improve their potency. Our major focus is on checkpoint blockade therapies, which are the most well-known and applicable immunotherapies.

Anxiety disorder is one of the most prevalent psychiatric disorders. The high prevalence of comorbid gastrointestinal disorders and anxiety, as well as various limitations in current therapy, have necessitated the search for alternative techniques. The Gut-Brain Axis is the connecting link between the gut and the brain. One of the reasons for the Gut-Brain Axis malfunction resulting in HPA axis stimulation and anxiety is intestinal barrier dysfunction. Gut microorganisms, lipopolysaccharides, and other factors can stimulate the disruption of this intestinal barrier. Tight junction proteins, the epithelial barrier, the mucosal membrane, the Toll-like receptor/Myeloid differentiation factor 88 pathway, the activated immune system, and the HPA axis could all be potential targets for anxiety caused by intestinal barrier disruption. Quercetin and Rebamipide, Berberine and Agomelatine, Angiotensin II receptor type 1 blockers, and Lubiprostone can act on these targets to provide an anxiolytic effect.

The gut microbiota are known to play an important role in maintaining the body’s homeostasis and increasing its immunoresistance. Their role has not been well defined in the course of SARS-CoV-2 infection. Aim: The aim of this study was to evaluate the pathogenetic relationship between gut microbiota, immunological reactivity disruption and microbiota pathologies with the new coronavirus infection's course in order to substantiate the use of current drugs correcting gut microbiota during the SARS-CoV-2 pandemic. Materials and Methods: Electronic databases of WHO Infection Control, Global Health, ScienceDirect, Elsevier, CDC infection diseases database, Google Academy, "Scientific electronic library eLIBRARY.RU", MEDLINE, CyberLeninka, Embase, PubMed-NCBI, RSCI, Scopus, and Cochrane Library were used for this analytical research. Results: The research results showed normal gut microbiota as one of the important components of a multilevel immune defense system. The intestinal microbiota support the notion of initial activation and readiness in order to induce a quick response to the invasion of pathogens, including RNA viruses, such as SARS-CoV-2. Current research suggests that the intestinal microbiota play an important role in the pathogenesis and predetermination of disease severity in COVID-19. By producing essential metabolites and neutralizing toxic substrates, symbionts regulate the functioning of all organs and systems, maintaining the body’s homeostasis and immunological responses. Intestinal microbiota disorders determine the postvaccination anti-COVID immunity's efficacy, specifically the susceptibility to SARS-CoV-2 and the severity of this infection. This is done by stimulating a local intestinal immune response via secretory immunoglobulins and the acquired immunity of the microbiome. The high prevalence of dysbiosis within the populous indicates the necessity of regular gut microbiota biocorrection during the SARS-CoV-2 pandemic. Our systematic review of current biopreparations correcting gut microbiota provides a valuable reference to the practicing clinicians to quickly specify and develop a wide variety of medicines, assess their capabilities, and choose the optimal treatment for patients at risk of SARS-CoV-2 infection. Conclusion: Current data support the notion that gut microflora biocorrection may help increase population immunity and preserve public health during the SARS-CoV-2 pandemic.

The author requested to add a co-author after the publication of the original article [1]. In this correction, the author has been added in the article entitled “GSK-3 Inhibitors in the Regulation and Control of Colon Carcinoma” in the journal “Current Drug Targets” 2021; 22(13), 1485-1495. Details of the error and a correction are provided here. The original editorial can be found online at 10.2174/1389450122666210204203950 We regret any errors and apologize to the readers. Original: Sitansu S. Nanda¹, Md Imran Hossain¹, Heongkyu Ju² and Dong Kee Yi¹,* ¹Department of Chemistry, Myongji University, Yongin, 03674, South Korea; ²Department of Physics, Gachon University, Seongnam-si, Gyeonggi-do, South Korea Corrected: Sitansu S. Nanda¹, Md Imran Hossain¹, Heongkyu Ju², Georgia C. Papaefthymiou³ and Dong Kee Yi¹,* ¹Department of Chemistry, Myongji University, Yongin, 03674, South Korea; ²Department of Physics, Gachon University, Seongnam-si, Gyeonggi-do, South Korea ³Department of Physics, Villanova University, Villanova, Pennsylvania19085, USA