scholarly journals Synthesis of Alginate-Curcumin Nanocomposite and Its Protective Role in Transgenic Drosophila Model of Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Wasi Khan ◽  
Braj Raj Singh ◽  
Alim H. Naqvi
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Bodies ◽  
Protective Role ◽  
Alpha Synuclein ◽  
Lower Permeability ◽  
Normal Human ◽  
Climbing Ability ◽  
The Brain

The genetic models in Drosophila provide a platform to understand the mechanism associated with degenerative diseases. The model for Parkinson's disease (PD) based on normal human alpha-synuclein (αS) expression was used in the present study. The aggregation of αS in brain leads to the formation of Lewy bodies and selective loss of dopaminergic neurons due to oxidative stress. Polyphenols generally have the reduced oral bioavailability, increased metabolic turnover, and lower permeability through the blood brain barrier. In the present study, the effect of synthesized alginate-curcumin nanocomposite was studied on the climbing ability of the PD model flies, lipid peroxidation, and apoptosis in the brain of PD model flies. The alginate-curcumin nanocomposite at final doses of 10−5, 10−3, and 10−1 g/mL was supplemented with diet, and the flies were allowed to feed for 24 days. A significant dose-dependent delay in the loss of climbing ability and reduction in the oxidative stress and apoptosis in the brain of PD model flies were observed. The results suggest that alginate-curcumin nanocomposite is potent in delaying the climbing disability of PD model flies and also reduced the oxidative stress as well as apoptosis in the brain of PD model flies.

Effect of polyherbal drug Majun falasfa on the transgenic Drosophila model of Parkinson’s Disease

2020 ◽  
Vol 07 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Falaq Naz ◽  
Mohammad Rashid
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Unani Medicine ◽  
Age Related ◽  
Drosophila Model ◽  
Climbing Ability ◽  
Transgenic Drosophila

Aim: The effect of Majun Falasfa (MF) was studied on the transgenic Drosophila expressing human alpha synuclein panneurally. Background: MF is a Unani medicine used for enhancing mental power and treating kidney, joint pains and urinary tract diseases. It is also use for phlegmatic diseases. It is also being used in age related dementia and to counter the effects of ageing. Methods: The equivalents of recommended dose for human were established for 20g of fly food i.e. 0.0014, 0.0028, 0.0042 and 0.0056g per 20g of diet. The PD flies were allowed to feed on it for 24 days before studying its effect on cognitive and oxidative stress parameters. Immunohistochemistry was also performed study the effect of MF on human alpha synuclein expression. Results: The exposure to MF increased the life span and improves the activity of PD flies. MF delayed the loss of climbing ability of PD flies. The exposure of PD flies to MF significantly reduced the oxidative stress and improves the antioxidant enzymes homeostasis compared to unexposed PD flies. The exposure to MF reduces the formation of Lewy bodies as is evident by immunohistochemistry. Conclusion: MF is potent in reducing the PD (Parkinson’s disease) symptoms being mimicked in the transgenic flies.

scholarly journals Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Peng Wang ◽  
Xin Li ◽  
Xuran Li ◽  
Weiwei Yang ◽  
Shun Yu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Alternative Pathway ◽  
Lewy Bodies ◽  
Normal Subjects ◽  
Alpha Synuclein ◽  
Phosphatase 2A ◽  
Alpha Synuclein Aggregation ◽  
The Brain ◽  
Neighboring Neuron

A pathological hallmark of Parkinson’s disease (PD) is formation of Lewy bodies in neurons of the brain. This has been attributed to the spread of α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more α-syn phosphorylation and oligomerization than plasma from normal subjects (NS). Compared with NS plasma, PD plasma added to primary neuron cultures caused more cell death in the presence of extracellular α-syn. This was supported by the observations that phosphorylated α-syn oligomers entered neurons, rapidly increased accumulated thioflavin S-positive inclusions, and induced a series of metabolic changes that included activation of polo-like kinase 2, inhibition of glucocerebrosidase and protein phosphatase 2A, and reduction of ceramide levels, all of which have been shown to promote α-syn phosphorylation and aggregation. We also analyzed neurotoxicity of α-syn oligomers relative to plasma from different patients. Neurotoxicity was not related to age or gender of the patients. However, neurotoxicity was positively correlated with H&Y staging score. The modification in the plasma may promote spreading of α-syn aggregates via an alternative pathway and accelerate progression of PD.

Lemon grass extract alleviates oxidative stress and delayed the loss of climbing ability in transgenic Drosophila model of Parkinson’s disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Falaq Naz ◽  
Mantasha I. ◽  
M. Shahid
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Positive Interaction ◽  
Lemon Grass ◽  
Drosophila Model ◽  
Climbing Ability ◽  
Transgenic Drosophila

Background: Parkinson’s Disease (PD) is characterized by the aggregation of α-synuclein, formation of Lewy bodies and the selective loss of dopaminergic neurons of mesencephalic substantia nigra pars compacta (SNC) with the debilitating motor symptoms. Introduction: The available treatment for PD provides symptomatic relief with no control on the progression of the disease. The treatment is also associated with several side effects. As the neurodegeneration in PD is also associated with the oxidative stress, antioxidants from plants could play an important role in reducing the PD symptoms. With this aim we decided to study the effect of Lemon grass extract (LGE) on the transgenic Drosophila model of PD expressing human alpha synuclein in the neurons. Methods: The PD flies allowed were allowed to feed on different doses of LGE established in diet for 24 days and then assayed for climbing ability and oxidative stress markers. The molecular docking study was also performed for citral (the component of the extract) and human α-synuclein. Results and discussion: A dose dependent significant improvement in the climbing ability and reduction in oxidative stress was observed in the PD flies exposed to LGE. In our earlier study on LGE, citral was found to be the main component of the extract by GC-MS analysis. The docking results also support the positive interaction between citral and human α-synuclein. Conclusion: The results suggests that LGE is potemnt in reducing the PD symptoms being mimicked in transgenic Drosophila.

scholarly journals The Gut–Brain Axis and Its Relation to Parkinson’s Disease: A Review

2022 ◽  
Vol 13 ◽  
Author(s):  
Emily M. Klann ◽  
Upuli Dissanayake ◽  
Anjela Gurrala ◽  
Matthew Farrer ◽  
Aparna Wagle Shukla ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Disease Diagnosis ◽  
Alpha Synuclein ◽  
Motor Symptoms ◽  
Abnormal Gait ◽  
Non Motor Symptoms ◽  
The Brain

Parkinson’s disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome–gut–brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome–gut–brain axis might play in the underlying pathological mechanisms of Parkinson’s disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson’s disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome–gut–brain axis in the context of Parkinson’s disease.

scholarly journals Fibroblast Growth Factor 20 Gene Polymorphism in Parkinson’s Disease in Asian Population: A Meta-Analysis

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 674
Author(s):  
Han-Lin Chiang ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Hon-Chung Fung ◽  
Chiung-Mei Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Meta Analysis ◽  
Lewy Bodies ◽  
Asian Population ◽  
Protective Role ◽  
Lewy Neurites ◽  
Chinese Populations ◽  
Study Results

Parkinson’s disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one of the risk loci located near the FGF20 gene that has been implicated in PD. The variation of FGF20 in the 3′ untranslated region was shown to increase α-synuclein expression. We examined the association of rs591323 with the risk of PD in a Taiwanese population and conducted a meta-analysis, including our study and two other studies from China, to further confirm the role of this SNP in Taiwanese/Chinese populations. A total of 586 patients with PD and 586 health controls (HCs) were included in our study. We found that the minor allele (A) and the AA + GA genotype under the dominant model are significantly less frequent in PD than in controls. The meta-analysis consisted of 1950 patients with PD and 2073 healthy controls from three studies. There was significant association between rs591323 and the risk of PD in the additive (Z = −3.96; p < 0.0001) and the dominant models (Z = −4.01; p < 0.0001). Our study results and the meta-analysis support the possible protective role of the rs591323 A allele in PD in Taiwanese/Chinese populations.

scholarly journals Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease

2016 ◽  
Vol 24 (7) ◽  
pp. 376-391 ◽  
Author(s):  
Emma Deas ◽  
Nunilo Cremades ◽  
Plamena R. Angelova ◽  
Marthe H.R. Ludtmann ◽  
Zhi Yao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Metal Ions ◽  
Neuronal Death ◽  
Alpha Synuclein

scholarly journals Alpha-synuclein alters the faecal viromes of rats in a gut-initiated model of Parkinson’s disease

2021 ◽  
Author(s):  
S. R. Stockdale ◽  
L. A. Draper ◽  
S. M. O’Donovan ◽  
W. Barton ◽  
O. O’Sullivan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Lewy Body ◽  
Neurological Disorder ◽  
Alpha Synuclein ◽  
Observational Period ◽  
Β Diversity ◽  
Potential Trigger ◽  
The Brain

AbstractParkinson’s disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into Lewy body aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes a potential trigger initiating the misfolding of α-syn. However, changes in the gut virome in response to α-syn alterations have not been investigated. In this study, we show longitudinal changes in the faecal virome of rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn. The virome β-diversity changes after α-syn treatment were compounded by the addition of LPS as an adjunct. Changes in the diversity of rat faecal viromes were observed after one month and did not resolve within the study’s five month observational period. Overall, these results suggest that microbiome alterations associated with PD may, partially, be reactive to host α-syn associated changes.

scholarly journals Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Epaminondas Doxakis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Clinical Manifestations ◽  
Alpha Synuclein ◽  
Circular Rnas ◽  
Age Related ◽  
And Function ◽  
The Brain

AbstractParkinson’s disease (PD) is a complex, age-related, neurodegenerative disease whose etiology, pathology, and clinical manifestations remain incompletely understood. As a result, care focuses primarily on symptoms relief. Circular RNAs (circRNAs) are a large class of mostly noncoding RNAs that accumulate with aging in the brain and are increasingly shown to regulate all aspects of neuronal and glial development and function. They are generated by the spliceosome through the backsplicing of linear RNA. Although their biological role remains largely unknown, they have been shown to regulate transcription and splicing, act as decoys for microRNAs and RNA binding proteins, used as templates for translation, and serve as scaffolding platforms for signaling components. Considering that they are stable, diverse, and detectable in easily accessible biofluids, they are deemed promising biomarkers for diagnosing diseases. CircRNAs are differentially expressed in the brain of patients with PD, and growing evidence suggests that they regulate PD pathogenetic processes. Here, the biogenesis, expression, degradation, and detection of circRNAs, as well as their proposed functions, are reviewed. Thereafter, research linking circRNAs to PD-related processes, including aging, alpha-synuclein dysregulation, neuroinflammation, and oxidative stress is highlighted, followed by recent evidence for their use as prognostic and diagnostic biomarkers for PD.

scholarly journals Subcellular orchestration of alpha-synuclein variants in Parkinson’s disease brains revealed by 3D multicolor STED microscopy

2018 ◽  
Author(s):  
Tim E. Moors ◽  
Christina A. Maat ◽  
Daniel Niedieker ◽  
Daniel Mona ◽  
Dennis Petersen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Bodies ◽  
Distribution Patterns ◽  
Alpha Synuclein ◽  
Label Free ◽  
Post Translational Modifications ◽  
Sted Microscopy ◽  
C Terminus

AbstractPost-translational modifications of alpha-synuclein (aSyn), particularly phosphorylation at Serine 129 (Ser129-p) and truncation of its C-terminus (CTT), have been implicated in Parkinson’s disease (PD) pathology. To gain more insight in the relevance of Ser129-p and CTT aSyn under physiological and pathological conditions, we investigated their subcellular distribution patterns in normal aged and PD brains using highly-selective antibodies in combination with 3D multicolor STED microscopy. We show that CTT aSyn localizes in mitochondria in PD patients and controls, whereas the organization of Ser129-p in a cytoplasmic network is strongly associated with pathology. Nigral Lewy bodies show an onion skin-like architecture, with a structured framework of Ser129-p aSyn and neurofilaments encapsulating CTT aSyn in their core, which displayed high content of proteins and lipids by label-free CARS microscopy. The subcellular phenotypes of antibody-labeled pathology identified in this study provide evidence for a crucial role of Ser129-p aSyn in Lewy body formation.

Sign in / Sign up

Export Citation Format

Share Document