A Potential Alternative against Neurodegenerative Diseases: Phytodrugs.
Ontology highlight
ABSTRACT:
SUBMITTER: Perez-Hernandez J
PROVIDER: S-EPMC4736801 | biostudies-other | 2016
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Natural antioxidants are a very large diversified family of molecules classified by activity (enzymatic or nonenzymatic), chemical-physical properties (e.g., hydrophilic or lipophilic), and chemical structure (e.g., vitamins, polyphenols, etc.). Research on natural antioxidants in various fields, such as pharmaceutics, nutraceutics, and cosmetics, is among the biggest challenges for industry and science. From a biomedical point of view, the scavenging activity of reactive oxygen species (ROS) makes them a potential tool for the treatment of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, dementia, and amyotrophic lateral sclerosis (ALS). In addition to the purified phytochemical compounds, a variety of natural extracts characterized by a complex mixture of antioxidants and anti-inflammatory molecules have been successfully exploited to rescue preclinical models of these diseases. Extracts derived from Ginkgo biloba, grape, oregano, curcumin, tea, and ginseng show multitherapeutic effects by synergically acting on different biochemical pathways. Furthermore, the reduced toxicity associated with many of these compounds limits the occurrence of side effects. The support of nanotechnology for improving brain delivery, controlling release, and preventing rapid degradation and excretion of these compounds is of fundamental importance. This review reports on the most promising results obtained on in vitro systems, in vivo models, and in clinical trials, by exploiting natural-derived antioxidant compounds and extracts, in their free form or encapsulated in nanocarriers.
| S-EPMC9352343 | biostudies-literature
Project description:Alkaloids are a type of natural compound possessing different pharmacological activities. Natural products, including alkaloids, which originate from plants, have emerged as potential protective agents against neurodegenerative disorders (NDDs) and chronic inflammations. A wide array of prescription drugs are used against these conditions, however, not free of limitations of potency, side effects, and intolerability. In the context of personalized medicine, further research on alkaloids to unravel novel therapeutic approaches in reducing complications is critical. In this review, a systematic survey was executed to collect the literature on alkaloids and their health complications, from which we found that majority of alkaloids exhibit anti-inflammatory action via nuclear factor-κB and cyclooxygenase-2 (COX-2), and neuroprotective interaction through acetylcholinesterase (AChE), COX, and β-site amyloid precursor protein activity. In silico ADMET and ProTox-II-related descriptors were calculated to predict the pharmacological properties of 280 alkaloids isolated from traditional medicinal plants towards drug development. Out of which, eight alkaloids such as tetrahydropalmatine, berberine, tetrandrine, aloperine, sinomenine, oxymatrine, harmine, and galantamine are found to be optimal within the categorical range when compared to nicotine. These alkaloids could be exploited as starting materials for novel drug synthesis or, to a lesser extent, manage inflammation and neurodegenerative-related complications.
| S-EPMC8926539 | biostudies-literature
Project description:Ceruloplasmin (CP) is the major copper transport protein in plasma, mainly produced by the liver. Glycosylphosphatidylinositol-linked CP (GPI-CP) is the predominant form expressed in astrocytes of the brain. A growing body of evidence has demonstrated that CP is an essential protein in the body with multiple functions such as regulating the homeostasis of copper and iron ions, ferroxidase activity, oxidizing organic amines, and preventing the formation of free radicals. In addition, as an acute-phase protein, CP is induced during inflammation and infection. The fact that patients with genetic disorder aceruloplasminemia do not suffer from tissue copper deficiency, but rather from disruptions in iron metabolism shows essential roles of CP in iron metabolism rather than copper. Furthermore, abnormal metabolism of metal ions and oxidative stress are found in other neurodegenerative diseases, such as Wilson's disease, Alzheimer's disease and Parkinson's disease. Brain iron accumulation and decreased activity of CP have been shown to be associated with neurodegeneration. We hypothesize that CP may play a protective role in neurodegenerative diseases. However, whether iron accumulation is a cause or a result of neurodegeneration remains unclear. Further research on molecular mechanisms is required before a consensus can be reached regarding a neuroprotective role for CP in neurodegeneration. This review article summarizes the main physiological functions of CP and the current knowledge of its role in neurodegenerative diseases.
| S-EPMC6712297 | biostudies-literature
Project description:The G protein-coupled receptor (GPCR) family of proteins comprises signaling proteins that mediate cellular responses to various hormones and neurotransmitters, and serves as a prime target for drug discovery. Towards our goal of discovering secondary metabolites from natural sources that can function as neuronal drugs, we evaluated the modulatory effect of eckol on various GPCRs via cell-based functional assays. In addition, we conducted in silico predictions to obtain molecular insights into the functional effects of eckol. Functional assays revealed that eckol had a concentration-dependent agonist effect on dopamine D? and D? receptors. The half maximal effective concentration (EC50) of eckol for the dopamine D? and D? receptors was 48.62 ± 3.21 and 42.55 ± 2.54 µM, respectively, while the EC50 values of dopamine as a reference agonist for these two receptors were 2.9 and 3.3 nM, respectively. In silico studies revealed that a low binding energy in addition to hydrophilic, hydrophobic, ??alkyl, and ??? T-shaped interactions are potential mechanisms by which eckol binds to the dopamine receptors to exert its agonist effects. Molecular dynamics (MD) simulation revealed that Phe346 of the dopamine receptors is important for binding of eckol, similar to eticlopride and dopamine. Our results collectively suggest that eckol is a potential D?/D? agonist for the management of neurodegenerative diseases, such as Parkinson's disease.
| S-EPMC6409773 | biostudies-literature
Project description:NRF2 acts by controlling gene expression, being the master regulator of the Phase II antioxidant response, and also being key to the control of neuroinflammation. NRF2 activity is regulated at several levels, including protein degradation by the proteasome, transcription, and post-transcription. The purpose of this review is to offer a concise and critical overview of the main mechanisms of NRF2 regulation and their actual or potential use as targets for the treatment of neurodegenerative diseases.
| S-EPMC7356958 | biostudies-literature
Project description:Retinal alterations have recently been associated with numerous neurodegenerative diseases. Rhodopsin is a G-protein coupled receptor found in the rod cells of the retina. As a biomarker associated with retinal thinning and degeneration, it bears potential in the early detection and monitoring of several neurodegenerative diseases. In this review article, we summarize the findings of correlations between rhodopsin and several neurodegenerative disorders as well as the potential of a novel technique, cSLO, in the quantification of rhodopsin.
| S-EPMC7175229 | biostudies-literature
Project description:MicroRNAs (miRNAs) are abundant, endogenous, short, noncoding RNAs that act as important post-transcriptional regulators of gene expression by base-pairing with their target mRNA. During the last decade, substantial knowledge has accumulated regarding the biogenesis of miRNAs, their molecular mechanisms and functional roles in a variety of cellular contexts. Altered expression of certain miRNA molecules in the brains of patients with neurodegenerative diseases such as Alzheimer and Parkinson suggests that miRNAs could have a crucial regulatory role in these disorders. Polymorphisms in miRNA target sites may also constitute an important determinant of disease risk. Additionally, emerging evidence points to specific miRNAs targeting and regulating the expression of particular proteins that are key to disease pathogenesis. Considering that the amount of these proteins in susceptible neuronal populations appears to be critical to neurodegeneration, miRNA-mediated regulation represents a new target of significant therapeutic prospects. In this review, the implications of miRNAs in several neurodegenerative disorders and their potential as therapeutic interventions are discussed.
| S-EPMC3268953 | biostudies-literature
Project description: Not available
| S-EPMC10154497 | biostudies-literature
Project description:BackgroundNeurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, Parkinson's disease (PD), spinal cerebellar ataxias, and spinal and bulbar muscular atrophy are described by slow and selective degeneration of neurons and axons in the central nervous system (CNS) and constitute one of the major challenges of modern medicine. Computeraided or in silico drug design methods have matured into powerful tools for reducing the number of ligands that should be screened in experimental assays.MethodsIn the present review, the authors provide a basic background about neurodegenerative diseases and in silico techniques in the drug research. Furthermore, they review the various in silico studies reported against various targets in neurodegenerative diseases, including homology modeling, molecular docking, virtual high-throughput screening, quantitative structure activity relationship (QSAR), hologram quantitative structure activity relationship (HQSAR), 3D pharmacophore mapping, proteochemometrics modeling (PCM), fingerprints, fragment-based drug discovery, Monte Carlo simulation, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design, support vector machines, and machine learning approaches.ResultsDetailed analysis of the recently reported case studies revealed that the majority of them use a sequential combination of ligand and structure-based virtual screening techniques, with particular focus on pharmacophore models and the docking approach.ConclusionNeurodegenerative diseases have a multifactorial pathoetiological origin, so scientists have become persuaded that a multi-target therapeutic strategy aimed at the simultaneous targeting of multiple proteins (and therefore etiologies) involved in the development of a disease is recommended in future.
| S-EPMC6080098 | biostudies-literature
Project description:Microglia activation is observed in various neurodegenerative diseases. Recent advances in single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified microglia in specific states correlate with pathological hallmarks and are associated with specific functions. Microglia both exert protective function by phagocytosing and clearing pathological protein aggregates and play detrimental roles due to excessive uptake of protein aggregates, which would lead to microglial phagocytic ability impairment, neuroinflammation, and eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes microglia into a pro-inflammatory phenotype and accelerates disease progression. Microglia also act as a mobile vehicle to propagate protein aggregates. Extracellular vesicles released from microglia and autophagy impairment in microglia all contribute to pathological progression and neurodegeneration. Thus, enhancing microglial phagocytosis, reducing microglial-mediated neuroinflammation, inhibiting microglial exosome synthesis and secretion, and promoting microglial conversion into a protective phenotype are considered to be promising strategies for the therapy of neurodegenerative diseases. Here we comprehensively review the biology of microglia and the roles of microglia in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and Huntington's disease. We also summarize the possible microglia-targeted interventions and treatments against neurodegenerative diseases with preclinical and clinical evidence in cell experiments, animal studies, and clinical trials.
| S-EPMC10514343 | biostudies-literature