Structure-based virtual screening of Trachyspermum ammi metabolites targeting acetylcholinesterase for Alzheimer's disease treatment.

In recent decades, Alzheimer's disease (AD) has garnered significant attention due to its rapid global prevalence. The cholinergic hypothesis posits that the degradation of acetylcholine by acetylcholinesterase (AChE) contributes to AD development. Despite existing anti-AChE drugs, their adverse side effects necessitate new agents.

Neurotrophic Effects of Ethanol Extracts on Hippocampal Neurons: Role of Anethole in Neurite Outgrowth and Synaptic Development.

Mill, commonly known as fennel, is an aromatic herb traditionally used for culinary and medicinal purposes, with potential therapeutic effects on neurological disorders. However, limited research has focused on its neurotrophic impact, particularly on neuronal maturation and synaptic development. This study investigates the neurotrophic effects of ethanol extracts (FVSE) on the maturation of rat primary hippocampal neurons.

Synthesis and elucidation of strained galactopyronose esters as selective cyclooxygenase-2 inhibitor: a comprehensive computational approach.

Cyclooxygenase-2 (COX-2) is critically implicated in various pathologies, including inflammation, cancer, disorders involving the nervous system, and multidrug resistance. In both academic and pharmaceutical research, the development of COX-2 selective drugs as anti-inflammatory and anti-tumor therapeutics is a key focus. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) have ulcerogenic, gastrointestinal adverse effects, and myocardial infarction risk, which resulted in their limited applications.

Differential Effects of the Processed and Unprocessed Garlic ( L.) Ethanol Extracts on Neuritogenesis and Synaptogenesis in Rat Primary Hippocampal Neurons.

Garlic ( L.) is an aromatic herb known for its culinary and medicinal uses for centuries. Both unprocessed (white) and processed (black) garlic are known to protect against the pathobiology of neurological disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), which has been attributed to their anti-inflammatory and antioxidant properties.

Gut Microbiota in Autophagy Regulation: New Therapeutic Perspective in Neurodegeneration.

Gut microbiota and the brain are related via a complex bidirectional interconnective network. Thus, intestinal homeostasis is a crucial factor for the brain, as it can control the environment of the central nervous system and play a significant role in disease progression. The link between neuropsychological behavior or neurodegeneration and gut dysbiosis is well established, but many involved pathways remain unknown.

Mechanistic study of Coriandrum sativum on neuritogenesis and synaptogenesis based on computationally guided in vitro analyses.

Ethnopharmacological Relevance: Acceleration of neurite outgrowth and halting neurodegeneration are the most critical factors that are negatively regulated in various neurodegenerative diseases or injuries in the central nervous system (CNS). Functional foods or nutrients are considered alternative sources of bioactive components to alleviate various CNS injuries by promoting neuritogenesis and synaptogenesis, while their exact molecular mechanism remains unexplored.

Aim Of The Study: Coriandrum sativum L.

design of epitope-based peptide vaccine against non-typhoidal through immunoinformatic approaches.

Non-typhoidal (NTS) is one of the leading bacterial causes of many invasive human infections with a high antibiotic resistance profile. With this concern, the current study aimed to design an effective epitope-based peptide vaccine against NTS species as a successive and substitutive protective measure of invasive NTS disease. To design rationally, the current study considered a comprehensive workflow combination of both immunoinformatics and molecular modeling approaches, including molecular docking and molecular dynamics (MD) simulation.

Natural Products Targeting Hsp90 for a Concurrent Strategy in Glioblastoma and Neurodegeneration.

Glioblastoma multiforme (GBM) is one of the most common aggressive, resistant, and invasive primary brain tumors that share neurodegenerative actions, resembling many neurodegenerative diseases. Although multiple conventional approaches, including chemoradiation, are more frequent in GBM therapy, these approaches are ineffective in extending the mean survival rate and are associated with various side effects, including neurodegeneration. This review proposes an alternative strategy for managing GBM and neurodegeneration by targeting heat shock protein 90 (Hsp90).

Dynamic insights into the effects of nonsynonymous polymorphisms (nsSNPs) on loss of TREM2 function.

Single nucleotide variations in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) are associated with many neurodegenerative diseases, including Nasu-Hakola disease (NHD), frontotemporal dementia (FTD), and late-onset Alzheimer's disease because they disrupt ligand binding to the extracellular domain of TREM2. However, the effects of nonsynonymous single nucleotide polymorphisms (nsSNPs) in TREM2 on disease progression remain unknown. In this study, we identified several high-risk nsSNPs in the TREM2 gene using various deleterious SNP predicting algorithms and analyzed their destabilizing effects on the ligand recognizing region of the TREM2 immunoglobulin (Ig) domain by molecular dynamics (MD) simulation.

Unveiling the effect of Withania somnifera on neuronal cytoarchitecture and synaptogenesis: A combined in vitro and network pharmacology approach.

Withania somnifera (WS), is known for its remarkable contribution in herbal medicine and Ayurveda, which is therapeutically applied to improve memory and anxiety in patients. However, the pharmacological details of this plant on memory boosting yet remained undefined. This study provides mechanistic insights on the effect of ethanol solution extract of the whole plant of WS (WSEE) on neuritogenesis by combining in vitro and in silico network pharmacology approaches.

Structural Consequence of Non-Synonymous Single-Nucleotide Variants in the N-Terminal Domain of LIS1.

Disruptive neuronal migration during early brain development causes severe brain malformation. Characterized by mislocalization of cortical neurons, this condition is a result of the loss of function of migration regulating genes. One known neuronal migration disorder is lissencephaly (LIS), which is caused by deletions or mutations of the (PAFAH1B1) gene that has been implicated in regulating the microtubule motor protein cytoplasmic dynein.

Targeting Estrogen Signaling in the Radiation-induced Neurodegeneration: A Possible Role of Phytoestrogens.

Radiation for medical use is a well-established therapeutic method with an excellent prognosis rate for various cancer treatments. Unfortunately, a high dose of radiation therapy comes with its own share of side effects, causing radiation-induced non-specific cellular toxicity; consequently, a large percentage of treated patients suffer from chronic effects during the treatment and even after the post-treatment. Accumulating data evidenced that radiation exposure to the brain can alter the diverse cognitive-related signaling and cause progressive neurodegeneration in patients because of elevated oxidative stress, neuroinflammation, and loss of neurogenesis.

Computational Insights into the Deleterious Impacts of Missense Variants on -Acetyl-d-glucosamine Kinase Structure and Function.

An enzyme of the mammalian amino-sugar metabolism pathway, -acetylglucosamine kinase (NAGK), that synthesizes -acetylglucosamine (GlcNAc)-6-phosphate, is reported to promote dynein functions during mitosis, axonal and dendritic growth, cell migration, and selective autophagy, which all are unrelated to its enzyme activity. As non-enzymatic structural functions can be altered by genetic variation, we made an effort in this study aimed at deciphering the pathological effect of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in gene. An integrated computational approach, including molecular dynamics (MD) simulation and protein-protein docking simulation, was used to identify the damaging nsSNPs and their detailed structural and functional consequences.

Black Cumin ( L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety.

Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin ( L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries.

Potential roles of natural products in the targeting of proteinopathic neurodegenerative diseases.

Defective proteostasis is associated with the gradual accumulations of misfolded proteins and is a hallmark of many age-associated neurodegenerative diseases. In the aged brain, maintenance of the proteostasis network presents a substantial challenge, and its loss contributes to the onset and progression of neurological diseases associated with cognitive decline due to the generation of toxic protein aggregates, a process termed 'proteinopathy'. Emerging evidence suggests that reversing proteinopathies by boosting proteostasis might provide an effective means of preventing neurodegeneration.

Centella asiatica promotes early differentiation, axodendritic maturation and synaptic formation in primary hippocampal neurons.

Background: Centella asiatica is a 'medhya-rasayana (nootrophic or memory booster)' herb that has been indicated in Ayurveda for improving memory function and treating dementia disorders. Although the neuroprotective effects of C. asiatica have been reported in earlier studies, the information on whether this nootropic herb could promote early differentiation and development of axon and dendrites in primary hippocampal neurons is currently limited.

Molecular simulation studies to reveal the binding mechanisms of shikonin derivatives inhibiting VEGFR-2 kinase.

Traditional vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors can manage angiogenesis; however, severe toxicity and resistance limit their long-term applications in clinical therapy. Shikonin (SHK) and its derivatives could be promising to inhibit the VEGFR-2 mediated angiogenesis, as they are reported to bind in the catalytic kinase domain with low affinity. However, the detailed molecular insights and binding dynamics of these natural inhibitors are unknown, which is crucial for potential SHK based lead design.

Emerging potential of cannabidiol in reversing proteinopathies.

The aberrant accumulation of disease-specific protein aggregates accompanying cognitive decline is a pathological hallmark of age-associated neurological disorders, also termed as proteinopathies, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. Along with oxidative stress and neuroinflammation, disruption in protein homeostasis (proteostasis), a network that constitutes protein surveillance system, plays a pivotal role in the pathobiology of these dementia disorders. Cannabidiol (CBD), a non-psychotropic phytocannabinoid of Cannabis sativa, is known for its pleiotropic neuropharmacological effects on the central nervous system, including the ability to abate oxidative stress, neuroinflammation, and protein misfolding.

Computational SNP Analysis and Molecular Simulation Revealed the Most Deleterious Missense Variants in the NBD1 Domain of Human ABCA1 Transporter.

The ATP-binding cassette transporter A1 (ABCA1) is a membrane-bound exporter protein involved in regulating serum HDL level by exporting cholesterol and phospholipids to load up in lipid-poor ApoA-I and ApoE, which allows the formation of nascent HDL. Mutations in the gene, when presents in both alleles, disrupt the canonical function of ABCA1, which associates with many disorders related to lipid transport. Although many studies have reported the phenotypic effects of a large number of ABCA1 variants, the pathological effect of non-synonymous polymorphisms (nsSNPs) in ABCA1 remains elusive.