Role of G-Proteins and GPCR-Mediated Signalling in Neuropathophysiology.

G-protein-coupled receptors (GPCRs) are activated by manifold neurotransmitters, and their activation, in turn, evokes slow synaptic transmission. They are profoundly related to numerous psychiatric and neurological disorders such as schizophrenia and Parkinson's disease. The significant malady indications for GPCR modulators demonstrate a change towards obesity, diabetes, and Alzheimer's disease, while other central nervous system disorders persist highly represented. GPR52, GPR6, and GPR8 are recognised as orphan GPCRs, co-exist either with both the dopamine D2 and D1 receptors in neurons of the basal ganglia or with the dopamine D2 receptor alone, and recommend that between these orphan receptors, GPR52 has the maximum potential of being a therapeutic psychiatric receptor. Genetically modified creature models and molecular biological investigations have suggested that these improved GPCRs could be potential therapeutic psychiatric receptors. In this perspective, the role of molecular targets in GPCR-mediated signalling has been discussed that would be novel drug design and discovery options for a scientist to elaborate previous knowledge with modern techniques.

An Insight into COVID-19 and Traditional Herbs: Bangladesh Perspective.

SARS-CoV-2 was first discovered in Wuhan in late 2019 and has since spread over the world, resulting in the present epidemic. Because targeted therapeutics are unavailable, scientists have the opportunity to discover new drugs or vaccines to counter COVID-19, and therefore a number of synthetic bioactive compounds are now being tested in clinical studies. Due to its broad therapeutic spectrum and low adverse effects, medicinal herbs have been used as traditional healing medication in those countries for ages. Due to a lack of synthetic bioactive antiviral medications, pharmaceutical and alternative therapies have been developed using a variety of herbal compositions. Due to the widespread availability of herbal and dietary products worldwide, people frequently use them. Notably, the majority of Bangladeshi people continue to use a variety of natural plants and herbs to treat various types of diseases. This review article discusses how previous research has shown that some herbs in Bangladesh have immunomodulatory and antiviral effects and how their active ingredients have been gathered. Even though FDA-approved medications and vaccines are available for the treatment of COVID-19, the purpose is to encourage the use of herbal medicine as immunomodulators and vaccine adjuvants for the treatment of COVID-19 prevention.

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation.

G protein-coupled receptors (GPCRs) are intricately involved in the conversion of extracellular feedback to intracellular responses. These specialized receptors possess a crucial role in neurological and psychiatric disorders. Most nonsensory GPCRs are active in almost 90% of complex brain functions. At the time of receptor phosphorylation, a GPCR pathway is essentially activated through a G protein signaling mechanism via a G protein-coupled receptor kinase (GRK). Dopamine, an important neurotransmitter, is primarily involved in the pathophysiology of several CNS disorders; for instance, bipolar disorder, schizophrenia, Parkinson's disease, and ADHD. Since dopamine, acetylcholine, and glutamate are potent neuropharmacological targets, dopamine itself has potential therapeutic effects in several CNS disorders. GPCRs essentially regulate brain functions by modulating downstream signaling pathways. GPR6, GPR52, and GPR8 are termed orphan GPCRs because they colocalize with dopamine D1 and D2 receptors in neurons of the basal ganglia, either alone or with both receptors. Among the orphan GPCRs, the GPR52 is recognized for being an effective psychiatric receptor. Various antipsychotics like aripiprazole and quetiapine mainly target GPCRs to exert their actions. One of the most important parts of signal transduction is the regulation of G protein signaling (RGS). These substances inhibit the activation of the G protein that initiates GPCR signaling. Developing a combination of RGS inhibitors with GPCR agonists may prove to have promising therapeutic potential. Indeed, several recent studies have suggested that GPCRs represent potentially valuable therapeutic targets for various psychiatric disorders. Molecular biology and genetically modified animal model studies recommend that these enriched GPCRs may also act as potential therapeutic psychoreceptors. Neurotransmitter and neuropeptide GPCR malfunction in the frontal cortex and limbic-related regions, including the hippocampus, hypothalamus, and brainstem, is likely responsible for the complex clinical picture that includes cognitive, perceptual, emotional, and motor symptoms. G protein and GPCR-mediated signaling play a critical role in developing new treatment options for mental health issues, and this study is aimed at offering a thorough picture of that involvement. For patients who are resistant to current therapies, the development of new drugs that target GPCR signaling cascades remains an interesting possibility. These discoveries might serve as a fresh foundation for the creation of creative methods for pharmacologically useful modulation of GPCR function.

In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases.

Exploring the Recent Trends in Management of Dementia and Frailty: Focus on Diagnosis and Treatment.

Dementia and frailty increase health adversities in older adults, which are topics of growing research interest. Frailty is considered to correspond to a biological syndrome associated with age. Frail patients may ultimately develop multiple dysfunctions across several systems, including stroke, transient ischemic attack, vascular dementia, Parkinson's disease, Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, cortico-basal degeneration, multiple system atrophy, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. Patients with dementia and frailty often develop malnutrition and weight loss. Rigorous nutritional, pharmacological, and non-pharmacological interventions generally are required for these patients, which is a challenging issue for healthcare providers. A healthy diet and lifestyle instigated at an early age can reduce the risk of frailty and dementia. For optimal treatment, accurate diagnosis involving clinical evaluation, cognitive screening, essential laboratory evaluation, structural imaging, functional neuroimaging, and neuropsychological testing is necessary. Diagnosis procedures best apply the clinical diagnosis, identifying the cause(s) and the condition(s) appropriate for treatment. The patient's history, caregiver's interview, physical examination, cognitive evaluation, laboratory tests, and structural imaging should best be involved in the diagnostic process. Varying types of physical exercise can aid the treatment of these disorders. Nutrition maintenance is a particularly significant factor, such as exceptionally high-calorie dietary supplements and a Mediterranean diet to support weight gain. The core purpose of this article is to investigate trends in the management of dementia and frailty, focusing on improving diagnosis and treatment. Substantial evidence builds the consensus that a combination of balanced nutrition and good physical activity is an integral part of treatment. Notably, more evidence-based medicine knowledge is required.