Dataset Information

Role of Plant-Derived Flavonoids and Their Mechanism in Attenuation of Alzheimer's and Parkinson's Diseases: An Update of Recent Data.

ABSTRACT: Neurodegeneration is a progressive loss of neuronal cells in certain regions of the brain. Most of the neurodegenerative disorders (NDDs) share the communal characteristic such as damage or reduction of various cell types typically including astrocytes and microglial activity. Several compounds are being trialed to treat NDDs but they possess solitary symptomatic advantages along with copious side effects. The finding of more enthralling and captivating compounds to suspend and standstill the pathology of NDDs will be considered as a hallmark of present times. Phytochemicals possess the potential to alternate the synthetic line of therapy against NDDs. The present review explores the potential efficacy of plant-derived flavonoids against most common NDDs including Alzheimer's disease (AD) and Parkinson's disease (PD). Flavonoids are biologically active phytochemicals which possess potential pharmacological effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic and anti-oxidant effects and are able to attenuate the pathology of various NDDs through down-regulating the nitric oxide (NO) production, by reducing the tumor necrosis factor-? (TNF-?), by reducing the excitotoxicity of superoxide as well as acting as tyrosine kinase (TK) and monoamine oxidase (MAO) inhibiting enzyme.

SUBMITTER: Hussain G

PROVIDER: S-EPMC6017497 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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Publications

Role of Plant-Derived Flavonoids and Their Mechanism in Attenuation of Alzheimer's and Parkinson's Diseases: An Update of Recent Data.

Hussain Ghulam G Zhang Longbin L Rasul Azhar A Anwar Haseeb H Sohail Muhammad Umar MU Razzaq Aroona A Aziz Nimra N Shabbir Asghar A Ali Muhammad M Sun Tao T

Molecules (Basel, Switzerland) 20180402 4

Neurodegeneration is a progressive loss of neuronal cells in certain regions of the brain. Most of the neurodegenerative disorders (NDDs) share the communal characteristic such as damage or reduction of various cell types typically including astrocytes and microglial activity. Several compounds are being trialed to treat NDDs but they possess solitary symptomatic advantages along with copious side effects. The finding of more enthralling and captivating compounds to suspend and standstill the pa ...[more]

PMID: 29614843

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Project description:Alzheimer's disease (AD) is characterized by the brain accumulation of A? peptides and by the presence of neurofibrillary tangles. A? is believed to play an important role in AD and it has been shown that certain flavonoids can affect A? production. Recently, it was suggested that the A? lowering properties of flavonoids are mediated by a direct inhibition the ?-secretase (BACE-1) activity, the rate limiting enzyme responsible for the production of A? peptides. Westernblots and ELISAs were employed to monitor the impact of flavonoids on amyloid precursor protein processing and A? production. A cell free chemoluminescent assay using human recombinant BACE-1 was used to assess the effect of flavonoids on BACE-1 activity. The effect of flavonoids on NF?B activation was determined by using a stable NF?B luciferase reporter cell line. Molecular docking simulations were performed to predict the binding of flavonoids to the BACE-1 catalytic site. Real time quantitative PCR was used to determine the effect of flavonoids on BACE-1 transcription. We show in a cell free assay that flavonoids are only weak inhibitors of BACE-1 activity. Docking simulation studies with different BACE-1 structures also suggest that flavonoids are poor BACE-1 inhibitors as they appear to adopt various docking poses in the active site pocket and have weak docking scores that differ as a function of the BACE-1 structures studied. Moreover, a weak correlation was observed between the effect of flavonoids on A? production in vitro and their ability to lower BACE-1 activity suggesting that the A? lowering properties of flavonoids in whole cells are not mediated via direct inhibition of BACE-1 activity. We found however a strong correlation between the inhibition of NF?B activation by flavonoids and their A? lowering properties suggesting that flavonoids inhibit A? production in whole cells via NF?B related mechanisms. As NF?B has been shown to regulate BACE-1 expression, we show that NF?B lowering flavonoids inhibit BACE-1 transcription in human neuronal SH-SY5Y cells. Altogether, our data suggest that flavonoids inhibit A? and sAPP? production by regulating BACE-1 expression and not by directly inhibiting BACE-1 activity.

Project description:Recent advances in large datasets analysis offer new insights to modern biology allowing system-level investigation of pathologies. Here we describe a novel computational method that exploits the ever-growing amount of "omics" data to shed light on Alzheimer's and Parkinson's diseases. Neurological disorders exhibit a huge number of molecular alterations due to a complex interplay between genetic and environmental factors. Classical reductionist approaches are focused on a few elements, providing a narrow overview of the etiopathogenic complexity of multifactorial diseases. On the other hand, high-throughput technologies allow the evaluation of many components of biological systems and their behaviors. Analysis of Parkinson's Disease (PD) and Alzheimer's Disease (AD) from a network perspective can highlight proteins or pathways common but differently represented that can be discriminating between the two pathological conditions, thus highlight similarities and differences.In this work we propose a strategy that exploits network community structure identified with a state-of-the-art network community discovery algorithm called InfoMap, which takes advantage of information theory principles. We used two similarity measurements to quantify functional and topological similarities between the two pathologies. We built a Similarity Matrix to highlight similar communities and we analyzed statistically significant GO terms found in clustered areas of the matrix and in network communities. Our strategy allowed us to identify common known and unknown processes including DNA repair, RNA metabolism and glucose metabolism not detected with simple GO enrichment analysis. In particular, we were able to capture the connection between mitochondrial dysfunction and metabolism (glucose and glutamate/glutamine).This approach allows the identification of communities present in both pathologies which highlight common biological processes. Conversely, the identification of communities without any counterpart can be used to investigate processes that are characteristic of only one of the two pathologies. In general, the same strategy can be applied to compare any pair of biological networks.

Dataset Information

Role of Plant-Derived Flavonoids and Their Mechanism in Attenuation of Alzheimer's and Parkinson's Diseases: An Update of Recent Data.

Publications

Role of Plant-Derived Flavonoids and Their Mechanism in Attenuation of Alzheimer's and Parkinson's Diseases: An Update of Recent Data.

Similar Datasets

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