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.

Low Molecular Weight Sulfated Chitosan: Neuroprotective Effect on Rotenone-Induced In Vitro Parkinson’s Disease

2018 ◽  
Vol 35 (3) ◽  
pp. 505-515 ◽  
Author(s):  
Venkatesan Manigandan ◽  
Jagatheesan Nataraj ◽  
Ramachandran Karthik ◽  
Thamilarasan Manivasagam ◽  
Ramachandran Saravanan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Molecular Weight ◽  
Parkinson's Disease ◽  
Neuroprotective Effect ◽  
Low Molecular Weight

scholarly journals Diagnosis of Parkinson’s Disease by A Metabolomics-Based Laboratory-Developed Test (LDT)

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 332 ◽  
Author(s):  
Petr G. Lokhov ◽  
Oxana P. Trifonova ◽  
Dmitry L. Maslov ◽  
Steven Lichtenberg ◽  
Elena E. Balashova
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Mass Spectrometry Analysis ◽  
Great Effort ◽  
Spectrometry Analysis ◽  
Yahr Scale ◽  
In Vitro Diagnostic ◽  
Stage 1

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured and used in the same laboratory (i.e., an in-house test). In this study, a metabolomics-based LDT was developed. This test involves a blood plasma preparation, direct-infusion mass spectrometry analysis with a high-resolution mass spectrometer, alignment and normalization of mass peaks using original algorithms, metabolite annotation by a biochemical context-driven algorithm, detection of overrepresented metabolic pathways and results in a visualization in the form of a pathway names cloud. The LDT was applied to detect early stage Parkinson’s disease (PD)—the diagnosis of which currently requires great effort due to the lack of available laboratory tests. In a case–control study (n = 56), the LDT revealed a statistically sound pattern in the PD-relevant pathways. Usage of the LDT for individuals confirmed its ability to reveal this pattern and thus diagnose PD at the early-stage (1–2.5 stages, according to Hoehn and Yahr scale). The detection of this pattern by LDT could diagnose PD with a specificity of 64%, sensitivity of 86% and an accuracy of 75%. Thus, this LDT can be used for further widespread testing.

scholarly journals Neuroprotection of Granulocyte Colony-Stimulating Factor for Early Stage Parkinson's Disease

2017 ◽  
Vol 26 (3) ◽  
pp. 409-416 ◽  
Author(s):  
Sheng-Tzung Tsai ◽  
Sung-Chao Chu ◽  
Shu-Hsin Liu ◽  
Cheng-Yoong Pang ◽  
Ting-Wen Hou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
In Vivo Studies ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Elevated Liver Enzymes ◽  
Stimulating Factor

Parkinson's disease (PD) is a slowly progressive neurodegenerative disease. Both medical and surgical choices provide symptomatic treatment. Granulocyte colony-stimulating factor (G-CSF), a conventional treatment for hematological diseases, has demonstrated its effectiveness in acute and chronic neurological diseases through its anti-inflammatory and antiapoptosis mechanisms. Based on previous in vitro and in vivo studies, we administered a lower dose (3.3 μg/kg) G-CSF injection for 5 days and six courses for 1 year in early-stage PD patients as a phase I trial. The four PD patient's mean unified PD rating scale motor scores in medication off status remained stable from 23 before the first G-CSF injection to 22 during the 2-year follow-up. 3,4-Dihydroxy-6-18F-fluoro-L-phenylalanine (18F-DOPA) positron emission tomography (PET) studies also revealed an annual 3.5% decrease in radiotracer uptake over the caudate nucleus and 7% in the putamen, both slower than those of previous reports of PD. Adverse effects included transient muscular–skeletal pain, nausea, vomiting, and elevated liver enzymes. Based on this preliminary report, G-CSF seems to alleviate disease deterioration for early stage PD patients. The effectiveness of G-CSF was possibly due to its amelioration of progressive dopaminergic neuron degeneration.

scholarly journals Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206536 ◽  
Author(s):  
Marcia Cristina T. dos Santos ◽  
Dieter Scheller ◽  
Claudia Schulte ◽  
Irene R. Mesa ◽  
Peter Colman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Early Stage ◽  
Disease Diagnosis ◽  
Cerebrospinal Fluid Proteins ◽  
Potential Biomarkers

scholarly journals Changes in multifinger interaction and coordination in Parkinson's disease

2012 ◽  
Vol 108 (3) ◽  
pp. 915-924 ◽  
Author(s):  
Jaebum Park ◽  
Yen-Hsun Wu ◽  
Mechelle M. Lewis ◽  
Xuemei Huang ◽  
Mark L. Latash
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Coordination ◽  
Feedforward Control ◽  
Early Stage ◽  
Isometric Force ◽  
Force Production ◽  
The Body ◽  
Total Force ◽  
Control Subjects

In this study, we tested several hypotheses related to changes in finger interaction and multifinger synergies during multifinger force production tasks in Parkinson's disease. Ten patients with Parkinson's disease, mostly early stage, and 11 healthy control subjects participated in the study. Synergies were defined as covaried adjustment of commands to fingers that stabilized the total force produced by the hand. Both Parkinson's disease patients and control subjects performed accurate isometric force production tasks with the fingers of both the dominant and nondominant hands. The Parkinson's disease patients showed significantly lower maximal finger forces and higher unintended force production (enslaving). These observations suggest that changes in supraspinal control have a major effect on finger individuation. The synergy indexes in the patients were weaker in both steady-state and cyclic force production tasks compared with the controls. These indexes also were stronger in the left (nondominant) hand in support of the dynamic-dominance hypothesis. Half of the patients could not perform the cyclic task at the highest frequency (2 Hz). Anticipatory adjustments of synergies prior to a quick force pulse production were delayed and reduced in the patients compared with the controls. Similar differences were observed between the asymptomatic hands of the patients with symptoms limited to one side of the body and matched hands of control subjects. Our study demonstrates that the elusive changes in motor coordination in Parkinson's disease can be quantified objectively, even in patients at a relatively early stage of the disease. The results suggest an important role of the basal ganglia in synergy formation and demonstrate a previously unknown component of impaired feedforward control in Parkinson's disease reflected in the reduced and delayed anticipatory synergy adjustments.

scholarly journals Plant- and Microbe-Derived Compounds Affect the Expression of Genes Encoding Antifungal Compounds in a Pseudomonad with Biocontrol Activity

2011 ◽  
Vol 77 (8) ◽  
pp. 2807-2812 ◽  
Author(s):  
Patrice de Werra ◽  
Aurélie Huser ◽  
Raphael Tabacchi ◽  
Christoph Keel ◽  
Monika Maurhofer
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Antifungal Compounds ◽  
Content Type ◽  
Expression Of Genes ◽  
Low Molecular Weight Compounds ◽  
Biocontrol Activity ◽  
Genes Encoding ◽  
Antifungal Genes

ABSTRACTWe have investigated the impacts of 63 different low-molecular-weight compounds, most of them plant derived, on thein vitroexpression of two antifungal biosynthetic genes by the plant-protecting rhizobacteriumPseudomonas fluorescensCHA0. The majority of the compounds tested affected the expression of one or both antifungal genes. This suggests that biocontrol activity in plant-beneficial pseudomonads is modulated by plant-bacterium signaling.

scholarly journals TLR2 and TLR4 in Parkinson’s disease pathogenesis: the environment takes a toll on the gut

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Anastazja M. Gorecki ◽  
Chidozie C. Anyaegbu ◽  
Ryan S. Anderton
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Intestinal Barrier ◽  
The Body ◽  
Enteric Neurons ◽  
Gut Dysfunction ◽  
Gut Homeostasis ◽  
The Brain

AbstractParkinson’s disease (PD) is an incurable, devastating disorder that is characterized by pathological protein aggregation and neurodegeneration in the substantia nigra. In recent years, growing evidence has implicated the gut environment and the gut-brain axis in the pathogenesis and progression of PD, especially in a subset of people who exhibit prodromal gastrointestinal dysfunction. Specifically, perturbations of gut homeostasis are hypothesized to contribute to α-synuclein aggregation in enteric neurons, which may spread to the brain over decades and eventually result in the characteristic central nervous system manifestations of PD, including neurodegeneration and motor impairments. However, the mechanisms linking gut disturbances and α-synuclein aggregation are still unclear. A plethora of research indicates that toll-like receptors (TLRs), especially TLR2 and TLR4, are critical mediators of gut homeostasis. Alongside their established role in innate immunity throughout the body, studies are increasingly demonstrating that TLR2 and TLR4 signalling shapes the development and function of the gut and the enteric nervous system. Notably, TLR2 and TLR4 are dysregulated in patients with PD, and may thus be central to early gut dysfunction in PD. To better understand the putative contribution of intestinal TLR2 and TLR4 dysfunction to early α-synuclein aggregation and PD, we critically discuss the role of TLR2 and TLR4 in normal gut function as well as evidence for altered TLR2 and TLR4 signalling in PD, by reviewing clinical, animal model and in vitro research. Growing evidence on the immunological aetiology of α-synuclein aggregation is also discussed, with a focus on the interactions of α-synuclein with TLR2 and TLR4. We propose a conceptual model of PD pathogenesis in which microbial dysbiosis alters the permeability of the intestinal barrier as well as TLR2 and TLR4 signalling, ultimately leading to a positive feedback loop of chronic gut dysfunction promoting α-synuclein aggregation in enteric and vagal neurons. In turn, α-synuclein aggregates may then migrate to the brain via peripheral nerves, such as the vagal nerve, to contribute to neuroinflammation and neurodegeneration typically associated with PD.

scholarly journals Biological Activity of the Tenebrionidae Beetle Antioxidant Complex in a Murine Neurotoxic Model of Parkinson's Disease

2021 ◽  
Author(s):  
Vladimir Kovalzon ◽  
Aleksandr Ambaryan ◽  
Aleksandr Revishchin ◽  
Galina Pavlova ◽  
Ekaterina Rybalkina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Biological Activity ◽  
Early Stage ◽  
Biologically Active ◽  
Human Neuroblastoma ◽  
Protein Nature ◽  
And Control

Abstract We have previously shown that the aqueous extract of the Ulomoides dermestoides darking beetle (the Tenebrionidae family) biomass contains a powerful complex of antioxidant substances of protein and non-protein nature. Considering the crucial role of ROS in the development of neurodegeneration, we set out to test the biological activity of this extract in a mouse neurotoxic model of Parkinson's disease. The beetle extracts were administrated continuously with food and their effects on parkinsonism caused by twice injected defoliant paraquat to experimental mice was evaluated. The motor activity of the animals was analyzed in behavioral tests using a rotarod and a vertical pole. The number of tyrosine hydroxylase-immunopositive neurons in the ventral part of the substantia nigra of the midbrains of experimental and control mice was studied by immunohistochemistry. In the model in vitro system with SH-SY5Y human neuroblastoma, the effect of the extracts on cell proliferation was examined in the absence and presence of the neurotoxin MPP+. The isolation of biologically active substances from raw biomass using cavitation effects made it possible to obtain extracts with protective properties in the model of an early stage of Parkinson's disease used in this study.

scholarly journals Molecular Docking Studies of Secondary Metabolites against Sequestosome-1 to Treat Parkinson Disease

2021 ◽  
Vol 9 (VI) ◽  
pp. 4456-4464
Author(s):  
Neeraj .
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rosmarinic Acid ◽  
The Body ◽  
In Vivo Studies ◽  
Axial Tomography ◽  
Low Level ◽  
Sequestosome 1

Parkinson's disease (PD) is one of the major progressive neurological disorders. It occurs due to a low level of a chemical substance in the brain known as Dopamine, which controls the muscle movements of the body. In many cases, PD occurs due to a low level of dopamine. PD generally appears in persons between the ages of 50 & 60. Some common symptoms of Parkinson's are slow movements, tremors, change in voice, depression, anxiety, hallucinations, psychosis, etc. Diagnosis of PD is done by CAT (Computerized Axial Tomography) scan or MRI (Magnetic Resonance Imaging, and DAT (Dopamine Transporter) scan. No specific cure for PD but Medication, Surgery, Adequate rest, exercise, and a balanced diet, and Several different drugs may help to relieve Parkinson's Disease (PD). According to the in silico study, we found that Rosmarinic Acid (RA) was the compound, which may inhibit the activities of Sequestosome-1. After in vitro and in vivo studies, Rosmarinic Acid may be an effective drug to control Parkinson's disease (PD).

Sign in / Sign up

Export Citation Format

Share Document