scholarly journals One-pot synthesis of a hydrogen peroxide-selective fluorogenic probe and its application in Parkinson's disease in vitro and vivo models

2020 ◽  
Vol 1 (5) ◽  
pp. 1448-1454 ◽  
Author(s):  
Yao Lu ◽  
Bo Peng ◽  
Xinghan Qiu ◽  
Xin Li ◽  
Zheng Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Hydrogen Peroxide ◽  
Parkinson's Disease ◽  
Multicomponent Reaction ◽  
Living Cells ◽  
Phosphate Ester ◽  
One Pot ◽  
Fluorogenic Probe ◽  
Abnormal Level

An abnormal level of hydrogen peroxide in neurons is strongly implicated in the progression of Parkinson’s disease. A one-pot multicomponent reaction has been utilized to synthesise phosphate ester-based probe for imaging of H2O2 in living cells and Drosophila PD model.

scholarly journals A novel fluorogenic probe for visualizing the hydrogen peroxide in Parkinson’s disease models

2020 ◽  
Vol 13 (03) ◽  
pp. 2050013
Author(s):  
Gaobin Zhang ◽  
Zheng Li ◽  
Fangjie Chen ◽  
Duoteng Zhang ◽  
Wenhui Ji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Hydrogen Peroxide ◽  
Parkinson's Disease ◽  
Living Cells ◽  
Emission Peak ◽  
Disease Models ◽  
Fluorogenic Probe ◽  
Highly Sensitive ◽  
Living Organisms

Parkinson’s disease (PD) is closely related to the oxidative stress induced by excess hydrogen peroxide (H2O2) in organisms. Developing an efficient method for noninvasive and real-time H2O2 detection is beneficial to investigate the role played by H2O2 in PD. In this work, a novel fluorogenic probe (CBH) for living organisms H2O2 detection has been designed, synthesized and characterized. The emission of CBH in PBS solution is very weak. However, when H2O2 was added, the fluorescence of CBH solution was sharply increased for 12-fold, accompanied by the emission peak blue-shifted from 600 to 530 nm. Moreover, the response of CBH to H2O2 is highly sensitive and selective and is not affected by various ROS/RNS, anions, cations, and amino acids. Based on the good performance of CBH for H2O2 detection, it has been successfully applied to visualizing the H2O2 concentration in living cells, Zebrafish and [Formula: see text]. elegans PD models.

α-synuclein implicated in Parkinson’s disease catalyses the formation of hydrogen peroxide in vitro

2001 ◽  
Vol 30 (10) ◽  
pp. 1163-1170 ◽  
Author(s):  
Stuart Turnbull ◽  
Brian J Tabner ◽  
Omar M.A El-Agnaf ◽  
Susan Moore ◽  
Yvonne Davies ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Hydrogen Peroxide ◽  
Parkinson's Disease

A novel pyrimidine based deep-red fluorogenic probe for detecting hydrogen peroxide in Parkinson's disease models

Talanta ◽  
2019 ◽  
Vol 199 ◽  
pp. 628-633 ◽  
Author(s):  
Xinghan Qiu ◽  
Chenqi Xin ◽  
Wenjing Qin ◽  
Zheng Li ◽  
Duoteng Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Hydrogen Peroxide ◽  
Parkinson's Disease ◽  
Disease Models ◽  
Fluorogenic Probe

Design, Optimization and Evaluation of Fast-Dissolving Oral Films of Ropinirole

2018 ◽  
Vol 11 (1) ◽  
pp. 3958-3967
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Srinivas A
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Good Alternative ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Onset Of Action ◽  
Disintegration Time ◽  
Peg 4000 ◽  
Oral Films

The main objective of this study was to develop fast dissolving oral films of ropinirole HCl to attain quick onset of action for the better management of Parkinson’s disease. Twenty-seven formulations (F1-F27) of ropinirole oral dissolving films by solvent-casting method using 33 response surface method by using HPMC E15, Maltodextrin PEG 4000 by using Design of experiment software. Formulations were evaluated for their physical characteristics, thickness, folding endurance, tensile strength, disintegration time, drug content uniformity and drug release characteristics and found to be within the limits. Among the prepared formulations F4 showed minimum disintegration time 11 sec, maximum drug was released i.e. 99.68 ± 1.52% of drug within 10 min when compared to the other formulations and finalized as optimized formulation. FTIR data revealed that no interactions takes place between the drug and polymers used in the optimized formulation. The in vitro dissolution profiles of marketed product and optimized formulation was compared and found to be the drug released was 92.77 ± 1.52 after 50 min. Therefore, it can be a good alternative to conventional ropinirole for immediate action. In vitro evaluation of the ropinirole fast dissolving films confirmed their potential as an innovative dosage form to improve delivery and quick onset of action of ropinirole. The oral dissolving film is considered to be potentially useful for the treatment of Parkinson’s disease where quick onset of action is desired

scholarly journals 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Manisha Singh ◽  
Manish Jain ◽  
Samrat Bose ◽  
Ashutosh Halder ◽  
Tapas Chandra Nag ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Dental Pulp ◽  
Neuronal Cells ◽  
Human Mesenchymal Stem Cells ◽  
Wistar Rat ◽  
Human Mscs ◽  
In Vitro Differentiation

AbstractOxysterols play vital roles in the human body, ranging from cell cycle regulation and progression to dopaminergic neurogenesis. While naïve human mesenchymal stem cells (hMSCs) have been explored to have neurogenic effect, there is still a grey area to explore their regenerative potential after in vitro differentiation. Hence, in the current study, we have investigated the neurogenic effect of 22(R)-hydroxycholesterol (22-HC) on hMSCs obtained from bone marrow, adipose tissue and dental pulp. Morphological and morphometric analysis revealed physical differentiation of stem cells into neuronal cells. Detailed characterization of differentiated cells affirmed generation of neuronal cells in culture. The percentage of generation of non-DA cells in the culture confirmed selective neurogenic potential of 22-HC. We substantiated the efficacy of these cells in neuro-regeneration by transplanting them into Parkinson’s disease Wistar rat model. MSCs from dental pulp had maximal regenerative effect (with 80.20 ± 1.5% in vitro differentiation efficiency) upon transplantation, as shown by various behavioural examinations and immunohistochemical tests. Subsequential analysis revealed that 22-HC yields a higher percentage of functional DA neurons and has differential effect on various tissue-specific primary human MSCs. 22-HC may be used for treating Parkinson’s disease in future with stem cells.

scholarly journals Multiple Pathways of LRRK2-G2019S/Rab10 Interaction in Dopaminergic Neurons

2021 ◽  
pp. 1-16
Author(s):  
Alison Fellgett ◽  
C. Adam Middleton ◽  
Jack Munns ◽  
Chris Ugbode ◽  
David Jaciuch ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Genetic Interaction ◽  
In Vitro Assays ◽  
Rab Proteins ◽  
Circadian Activity ◽  
Loss Of Function ◽  
Lrrk2 G2019s

Background: Inherited mutations in the LRRK2 protein are the common causes of Parkinson’s disease, but the mechanisms by which increased kinase activity of mutant LRRK2 leads to pathological events remain to be determined. In vitro assays (heterologous cell culture, phospho-protein mass spectrometry) suggest that several Rab proteins might be directly phosphorylated by LRRK2-G2019S. An in vivo screen of Rab expression in dopaminergic neurons in young adult Drosophila demonstrated a strong genetic interaction between LRRK2-G2019S and Rab10. Objective: To determine if Rab10 is necessary for LRRK2-induced pathophysiological responses in the neurons that control movement, vision, circadian activity, and memory. These four systems were chosen because they are modulated by dopaminergic neurons in both humans and flies. Methods: LRRK2-G2019S was expressed in Drosophila dopaminergic neurons and the effects of Rab10 depletion on Proboscis Extension, retinal neurophysiology, circadian activity pattern (‘sleep’), and courtship memory determined in aged flies. Results: Rab10 loss-of-function rescued LRRK2-G2019S induced bradykinesia and retinal signaling deficits. Rab10 knock-down, however, did not rescue the marked sleep phenotype which results from dopaminergic LRRK2-G2019S. Courtship memory is not affected by LRRK2, but is markedly improved by Rab10 depletion. Anatomically, both LRRK2-G2019S and Rab10 are seen in the cytoplasm and at the synaptic endings of dopaminergic neurons. Conclusion: We conclude that, in Drosophila dopaminergic neurons, Rab10 is involved in some, but not all, LRRK2-induced behavioral deficits. Therefore, variations in Rab expression may contribute to susceptibility of different dopaminergic nuclei to neurodegeneration seen in people with Parkinson’s disease.

scholarly journals Grafts Derived from an α-Synuclein Triplication Patient Mediate Functional Recovery but Develop Disease-Associated Pathology in the 6-OHDA Model of Parkinson’s Disease

2020 ◽  
pp. 1-14
Author(s):  
Shelby Shrigley ◽  
Fredrik Nilsson ◽  
Bengt Mattsson ◽  
Alessandro Fiorenzano ◽  
Janitha Mudannayake ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Functional Recovery ◽  
Embryonic Stem ◽  
Hesc Line ◽  
Alternative Source ◽  
And Function

Background: Human induced pluripotent stem cells (hiPSCs) have been proposed as an alternative source for cell replacement therapy for Parkinson’s disease (PD) and they provide the option of using the patient’s own cells. A few studies have investigated transplantation of patient-derived dopaminergic (DA) neurons in preclinical models; however, little is known about the long-term integrity and function of grafts derived from patients with PD. Objective: To assess the viability and function of DA neuron grafts derived from a patient hiPSC line with an α-synuclein gene triplication (AST18), using a clinical grade human embryonic stem cell (hESC) line (RC17) as a reference control. Methods: Cells were differentiated into ventral mesencephalic (VM)-patterned DA progenitors using an established GMP protocol. The progenitors were then either terminally differentiated to mature DA neurons in vitro or transplanted into 6-hydroxydopamine (6-OHDA) lesioned rats and their survival, maturation, function, and propensity to develop α-synuclein related pathology, were assessed in vivo. Results: Both cell lines generated functional neurons with DA properties in vitro. AST18-derived VM progenitor cells survived transplantation and matured into neuron-rich grafts similar to the RC17 cells. After 24 weeks, both cell lines produced DA-rich grafts that mediated full functional recovery; however, pathological changes were only observed in grafts derived from the α-synuclein triplication patient line. Conclusion: This data shows proof-of-principle for survival and functional recovery with familial PD patient-derived cells in the 6-OHDA model of PD. However, signs of slowly developing pathology warrants further investigation before use of autologous grafts in patients.

scholarly journals Holistic Metabolomic Laboratory-Developed Test (LDT): Development and Use for the Diagnosis of Early-Stage Parkinson’s Disease

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 14
Author(s):  
Petr G. Lokhov ◽  
Dmitry L. Maslov ◽  
Steven Lichtenberg ◽  
Oxana P. Trifonova ◽  
Elena E. Balashova
Keyword(s):  
Parkinson’S Disease ◽  
Molecular Weight ◽  
Parkinson's Disease ◽  
High Resolution Mass Spectrometry ◽  
Early Stage ◽  
Disease Diagnosis ◽  
The Body ◽  
Low Molecular Weight ◽  
Low Molecular Weight Compounds

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is developed and used within a single laboratory. The holistic metabolomic LDT integrating the currently available data on human metabolic pathways, changes in the concentrations of low-molecular-weight compounds in the human blood during diseases and other conditions, and their prevalent location in the body was developed. That is, the LDT uses all of the accumulated metabolic data relevant for disease diagnosis and high-resolution mass spectrometry with data processing by in-house software. In this study, the LDT was applied to diagnose early-stage Parkinson’s disease (PD), which currently lacks available laboratory tests. The use of the LDT for blood plasma samples confirmed its ability for such diagnostics with 73% accuracy. The diagnosis was based on relevant data, such as the detection of overrepresented metabolite sets associated with PD and other neurodegenerative diseases. Additionally, the ability of the LDT to detect normal composition of low-molecular-weight compounds in blood was demonstrated, thus providing a definition of healthy at the molecular level. This LDT approach as a screening tool can be used for the further widespread testing for other diseases, since ‘omics’ tests, to which the metabolomic LDT belongs, cover a variety of them.

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