[3H]inositol 1,4,5-trisphosphate binding sites in human brain: Binding characteristics and changes in the brain of patients with Parkinson's disease

Parkinson’s disease (PD) exhibits the second-highest rate of mortality among neurodegenerative diseases. PD is difficult to diagnose and treat due to its polygenic nature. In recent years, numerous studies have established a correlation between this disease and miRNA expression; however, it remains necessary to determine the quantitative characteristics of the interactions between miRNAs and their target genes. In this study, using novel bioinformatics approaches, the quantitative characteristics of the interactions between miRNAs and the mRNAs of candidate PD genes were established. Of the 6,756 miRNAs studied, more than one hundred efficiently bound to mRNA of 61 candidate PD genes. The miRNA binding sites (BS) were located in the 5′-untranslated region (5′UTR), coding sequence (CDS) and 3′-untranslated region (3′UTR) of the mRNAs. In the mRNAs of many genes, the locations of miRNA BS with overlapping nucleotide sequences (clusters) were identified. Such clusters substantially reduced the proportion of nucleotide sequences of miRNA BS in the 5′UTRs, CDSs, and 3′UTRs. The organization of miRNA BS into clusters leads to competition among miRNAs to bind mRNAs. Differences in the binding characteristics of miRNAs to the mRNAs of genes expressed at different rates were identified. Single miRNA BS, polysites for the binding for one miRNA, and multiple BS for two or more miRNAs in one mRNA were identified. Evolutionary changes in the BS of miRNAs and their clusters in 5′UTRs, CDSs and 3′UTRs of mRNA of orthologous candidate PD genes were established. Based on the quantitative characteristics of the interactions between miRNAs and mRNAs candidate PD genes, several associations recommended as markers for the diagnosis of PD.

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Sulfonylurea binding sites in normal human brain and in Parkinson's disease, progressive supranuclear palsy and Huntington's disease

Brain Research ◽

10.1016/0006-8993(94)90938-5 ◽

1994 ◽

Vol 642 (1-2) ◽

pp. 327-333 ◽

Cited By ~ 8

Author(s):

Sophie Holemans ◽

France Javoy-Agid ◽

Yves Agid ◽

Freddy De Paermentier ◽

E. Christian Laterre ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Human Brain ◽

Huntington's Disease ◽

Progressive Supranuclear Palsy ◽

Huntington’S Disease ◽

Binding Sites ◽

Normal Human Brain ◽

Normal Human

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Gene expression analysis in modeling Parkinson’s disease

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.04.103-104 ◽

2020 ◽

pp. 103-104

Author(s):

М.М. Руденок ◽

А.Х. Алиева ◽

А.А. Колачева ◽

М.В. Угрюмов ◽

П.А. Сломинский ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Systemic Disease ◽

Molecular Genetic ◽

Presymptomatic Stage ◽

Whole Transcriptome Analysis ◽

Whole Transcriptome ◽

The Brain ◽

Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

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Faculty Opinions recommendation of Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736045520.793568974 ◽

2019 ◽

Author(s):

Y Peng Loh ◽

Ashley Xiao

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Brain Models ◽

The Brain

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Pharmacological treatment with L-DOPA may reduce striatal dopamine transporter binding in in vivo imaging studies

Nuklearmedizin ◽

10.3413/nukmed-0764-15-08 ◽

2016 ◽

Vol 55 (01) ◽

pp. 21-28 ◽

Cited By ~ 4

Author(s):

C. Antke ◽

H. Hautzel ◽

H.-W. Mueller ◽

S. Nikolaus

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Binding Sites ◽

Human Subjects ◽

Synaptic Cleft ◽

Presynaptic Terminal ◽

Imaging Studies ◽

Psychiatric Conditions ◽

Da Release

SummaryNumerous neurologic and psychiatric conditions are treated with pharmacological compounds, which lead to an increase of synaptic dopamine (DA) levels. One example is the DA precursor L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted to DA in the presynaptic terminal. If the increase of DA concentrations in the synaptic cleft leads to competition with exogenous radioligands for presynaptic binding sites, this may have implications for DA transporter (DAT) imaging studies in patients under DAergic medication.This paper gives an overview on those findings, which, so far, have been obtained on DAT binding in human Parkinson’s disease after treatment with L-DOPA. Findings, moreover, are related to results obtained on rats, mice or non-human primates. Results indicate that DAT imaging may be reduced in the striata of healthy animals, in the unlesioned striata of animal models of unilateral Parkinson’s disease and in less severly impaired striata of Parkinsonian patients, if animal or human subjects are under acute or subchronic treatment with L-DOPA. If also striatal DAT binding is susceptible to alterations of synaptic DA levels, this may allow to quantify DA reuptake in analogy to DA release by assessing the competition between endogenous DA and the administered exogenous DAT radioligand.

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Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612826666200128145124 ◽

2020 ◽

Vol 26 (37) ◽

pp. 4721-4737 ◽

Cited By ~ 4

Author(s):

Bhumika Kumar ◽

Mukesh Pandey ◽

Faheem H. Pottoo ◽

Faizana Fayaz ◽

Anjali Sharma ◽

...

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Side Effects ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Brain Targeting ◽

Neural Cells ◽

Blood Brain ◽

The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

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Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612825666191113103537 ◽

2020 ◽

Vol 25 (42) ◽

pp. 4510-4522 ◽

Cited By ~ 5

Author(s):

Biancamaria Longoni ◽

Irene Fasciani ◽

Shivakumar Kolachalam ◽

Ilaria Pietrantoni ◽

Francesco Marampon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Potential Role ◽

Current Knowledge ◽

Biological Fluids ◽

Cell Communication ◽

Target Cells ◽

Cellular Debris ◽

The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

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