Up-regulation of miR-409-3p in cerebrospinal fluid of Parkinson's disease reduce the apoptosis of dopamine neurons

2020 ◽  
Vol 79 ◽  
pp. e10-e11
Author(s):  
X. Tan ◽  
J. Tan ◽  
F. Ming ◽  
L. Lv ◽  
H. Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Dopamine Neurons

scholarly journals Dopamine Neuron Challenge Test for early detection of Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jingheng Zhou ◽  
Jicheng Li ◽  
Amy B. Papaneri ◽  
Nicholas P. Kobzar ◽  
Guohong Cui
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Diagnostic Tests ◽  
Dopamine Release ◽  
Challenge Test ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
High Risk Population ◽  
Clinical Onset

AbstractDiagnosing Parkinson’s disease (PD) before the clinical onset proves difficult because the hallmark PD symptoms do not manifest until more than 60% of dopamine neurons in the substantia nigra pars compacta have been lost. Here we show that, by evoking a transient dopamine release and subsequently measuring the levels of dopamine metabolites in the cerebrospinal fluid and plasma, a hypodopaminergic state can be revealed when less than 30% of dopamine neurons are lost in mouse PD models. These findings may lead to sensitive and practical screening and diagnostic tests for detecting early PD in the high-risk population.

Neopterin and Cytokines in Hereditary Dystonia and Parkinson's Disease

Pteridines ◽  
1999 ◽  
Vol 10 (1) ◽  
pp. 5-13 ◽  
Author(s):  
T. Nagatsu ◽  
H. Ichinose ◽  
M. Mogi ◽  
A. Togari
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Dopamine Neurons ◽  
Gtp Cyclohydrolase I ◽  
Gtp Cyclohydrolase ◽  
Nigrostriatal Dopamine ◽  
Nigrostriatal Dopamine Neurons

βBoth neopterin and biopterin concentrations in cerebrospinal fluid from patients with Parkinson's disease, in which the nigrostriatal dopamine neurons degenerate, were lower than those from age-matched older control subjects. However, the decrease in biopterin was more marked than that in neopterin, resulting in the increase in the neopterin/ biopterin ratio in Parkinson's disease. These results suggests that neopterin in cerebrospinal fluid in Parkinson's disease may partly be derived from immunoactivated glial cells, besides catecholamine or serotonin n eurons including nigrostriatal dopamine neurons. In accordance to this hypothesis, cytokines (TNF-α, IL-1, IL-2 , IL-6, EGF, TGF-α, TGF-β1) were found to be increased in the striatum and/or in cerebrospinal fluid. The increment of cytokines in the brain in Parkinson's disease may be related to the mechanism of neurodegeneration of dopaminergic neurons in Parkinson's disease . In contrast to Parkinson's disease, in hereditary progressive dystonia/ dopa-responsive dystonia, which is a dopamine deficiency caused by mutations in GTP cyclohydrolase I without neuronal cell death (Segawa's disease), neopterin and biopterin in cerebrospinal fluid decreases in parallel owing to the decreased activity in GTP cyclohydrolase I .

scholarly journals MicroRNA-409-3p Targeting at ATXN3 Reduces the Apoptosis of Dopamine Neurons Based on the Profile of miRNAs in the Cerebrospinal Fluid of Early Parkinson’s Disease

2022 ◽  
Vol 9 ◽  
Author(s):  
Xuling Tan ◽  
Junjian Hu ◽  
Fengyu Ming ◽  
Lingling Lv ◽  
Weiqian Yan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Dopamine Neurons ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Real Time Quantitative Pcr ◽  
Gene Assay ◽  
Next Generation Sequencing Ngs ◽  
Early Parkinson’S Disease

Precise recognition of early Parkinson’s disease (PD) has always been a challenging task requiring more feasible biomarkers to be integrated to improve diagnostic accuracy. MicroRNAs (miRNAs) of cerebrospinal fluid (CSF) are believed to be potential and promising candidate biomarkers for PD. However, the role of altered miRNAs of CSF play in PD is unclear. Here, we recruited patients with early stages of PD and controls to analyze the expression of miRNA in CSF by the Next Generation Sequencing (NGS). Furthermore, we tested the levels of these miRNA in SH-SY5Y cells treated with MPP+ using real-time quantitative PCR. We found 21 miRNAs were upregulated in CSF of early PD patients and miR-409-3p, one of the identified 21 miRNAs, was further confirmed in SH-SY5Y cells treated with MPP+. Also, more cells survived in the overexpression of the miR-409-3p group when SH-SY5Y cells and mice were treated with MPP+ and MPTP, respectively. Mechanistically, we demonstrated the binding of miR-409-3p and 3’UTR of ATXN3 through a dual luciferase reporter gene assay. Moreover, miR-409-3p mimic reduced the aggregation of polyglutamine-expanded mutant of ATXN3 and apoptosis. Our results provide experimental evidence for miR-409-3p in CSF as a diagnostic marker of PD.

Cerebrospinal Fluid from Patients with Parkinson's Disease Alters the Survival of Dopamine Neurons in Mesencephalic Culture

1994 ◽  
Vol 126 (1) ◽  
pp. 15-24 ◽  
Author(s):  
S.J. Yu ◽  
E.S. Lo ◽  
E.J. Cochran ◽  
D.H. Lin ◽  
C.J. Faselis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Dopamine Neurons

scholarly journals α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer Dagra ◽  
Douglas R. Miller ◽  
Min Lin ◽  
Adithya Gopinath ◽  
Fatemeh Shaerzadeh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Activity ◽  
Dopaminergic Neurons ◽  
Prolonged Exposure ◽  
D2 Receptor ◽  
Neuronal Firing ◽  
Dopamine Neurons ◽  
Loss Of Function ◽  
Therapeutic Implications

AbstractPathophysiological damages and loss of function of dopamine neurons precede their demise and contribute to the early phases of Parkinson’s disease. The presence of aberrant intracellular pathological inclusions of the protein α-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson’s disease. We employed molecular biology, electrophysiology, and live-cell imaging to investigate how excessive α-synuclein expression alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission in cultured dopamine neurons conditionally expressing GCaMP6f. We found that overexpression of α-synuclein in mouse (male and female) dopaminergic neurons altered neuronal firing properties, calcium dynamics, dopamine release, protein expression, and morphology. Moreover, prolonged exposure to the D2 receptor agonist, quinpirole, rescues many of the alterations induced by α-synuclein overexpression. These studies demonstrate that α-synuclein dysregulation of neuronal activity contributes to the vulnerability of dopaminergic neurons and that modulation of D2 receptor activity can ameliorate the pathophysiology. These findings provide mechanistic insights into the insidious changes in dopaminergic neuronal activity and neuronal loss that characterize Parkinson’s disease progression with significant therapeutic implications.

scholarly journals Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson's Disease

2021 ◽  
Author(s):  
Thomas Kremer ◽  
Kirsten I. Taylor ◽  
Juliane Siebourg‐Polster ◽  
Thomas Gerken ◽  
Andreas Staempfli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Longitudinal Analysis ◽  
Early Parkinson’S Disease ◽  
Neurotransmitter Metabolites

scholarly journals Endoplasmic Reticulum Stress Regulators: New Drug Targets for Parkinson’s Disease

2021 ◽  
pp. 1-10
Author(s):  
Vera Kovaleva ◽  
Mart Saarma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Er Stress ◽  
Protein Misfolding ◽  
Drug Targets ◽  
Dopamine Neurons ◽  
Drug Candidates ◽  
The Unfolded Protein Response

Parkinson’s disease (PD) pathology involves progressive degeneration and death of vulnerable dopamine neurons in the substantia nigra. Extensive axonal arborisation and distinct functions make this type of neurons particularly sensitive to homeostatic perturbations, such as protein misfolding and Ca2 + dysregulation. Endoplasmic reticulum (ER) is a cell compartment orchestrating protein synthesis and folding, as well as synthesis of lipids and maintenance of Ca2 +-homeostasis in eukaryotic cells. When misfolded proteins start to accumulate in ER lumen the unfolded protein response (UPR) is activated. UPR is an adaptive signalling machinery aimed at relieving of protein folding load in the ER. When UPR is chronic, it can either boost neurodegeneration and apoptosis or cause neuronal dysfunctions. We have recently discovered that mesencephalic astrocyte-derived neurotrophic factor (MANF) exerts its prosurvival action in dopamine neurons and in animal model of PD through the direct binding to UPR sensor inositol-requiring protein 1 alpha (IRE1α) and attenuation of UPR. In line with this, UPR targeting resulted in neuroprotection and neurorestoration in various preclinical PD animal models. Therefore, growth factors (GFs), possessing both neurorestorative activity and restoration of protein folding capacity are attractive as drug candidates for PD treatment especially their blood-brain barrier penetrating analogs and small molecule mimetics. In this review, we discuss ER stress as a therapeutic target to treat PD; we summarize the existing preclinical data on the regulation of ER stress for PD treatment. In addition, we point out the crucial aspects for successful clinical translation of UPR-regulating GFs and new prospective in GFs-based treatments of PD, focusing on ER stress regulation.

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