Intestinal flora imbalance affects the prognosis of Parkinson's disease by regulating the expression of fecal microRNA-146a and GDNF: A Preliminary Study

2021 ◽  
Author(s):  
Hongchun Wei ◽  
Yinbao Hu ◽  
Liqing Yang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intestinal Flora ◽  
Lactobacillus Rhamnosus ◽  
Inhibitory Effect ◽  
Luciferase Assay ◽  
Regulatory Relationship ◽  
Tissue Samples ◽  
Protein Levels

IntroductionThere is mounting evidence showing the association between the gut microbiome and Parkinson’s disease (PD). In this study, we aimed to explore the role of intestinal flora imbalance in the progression of PD and the underlying molecular mechanism involving the regulatory relationship between miR-146a and glial cell line–derived neurotrophic factor (GDNF).Material and methodsA total of 42 PD patients were recruited in this study and grouped according to their prognosis. Real-time PCR, computational analysis and luciferase assay were carried out to explore the role of miR-146a and GDNF in PD patients as well as the regulatory relationship between the expression of miR-146a and GDNF. A rat model was used to study the effect of intestinal flora imbalance by treating the rats with Lactobacillus rhamnosus NCDC17.ResultsA lower count of total lactobaccilus and B. fragilis may predict the progression of PD. GDNF was identified as a virtual target gene of miR-146a, whose expression in fecal, plasma and cerebral tissue samples was significantly reduced in PD patients. In addition, the presence of miR-146a precursors and GDNF siRNA significantly reduced the mRNA and protein levels of GDNF in SH-SY5Y and U251 cells, and the inhibitory effect of miR-146a precursors on GDNF expression was similar to that of GDNF siRNA.ConclusionsTaken together, the findings of this study demonstrated that GDNF is a key factor involved in the prognosis of PD. we suggested that the administration of Lactobacillus rhamnosus NCDC17 promoted the pathogenesis of PD by regulating the expression of miR-146a and GDNF in the brain.

scholarly journals Magnolol Protects against MPTP/MPP+-Induced Toxicity via Inhibition of Oxidative Stress inIn VivoandIn VitroModels of Parkinson’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Akiko Muroyama ◽  
Aya Fujita ◽  
Cheng Lv ◽  
Shota Kobayashi ◽  
Yoshiyasu Fukuyama ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oxygen Species ◽  
Protective Effects ◽  
Human Neuroblastoma ◽  
Protein Levels ◽  
Mptp Treatment

The aim of this study is to investigate the role of magnolol in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-) induced neurodegeneration in mice and 1-methyl-4-phenylpyridinium ion-(MPP+-) induced cytotoxicity to human neuroblastoma SH-SY5Y cells and to examine the possible mechanisms. Magnolol (30 mg/kg) was orally administered to C57BL/6N mice once a day for 4 or 5 days either before or after MPTP treatment. Western blot analysis revealed that MPTP injections substantially decreased protein levels of dopamine transporter (DAT) and tyrosine hydroxylase (TH) and increased glial fibrillary acidic protein (GFAP) levels in the striatum. Both treatments with magnolol significantly attenuated MPTP-induced decrease in DAT and TH protein levels in the striatum. However, these treatments did not affect MPTP-induced increase in GFAP levels. Moreover, oral administration of magnolol almost completely prevented MPTP-induced lipid peroxidation in the striatum. In human neuroblastoma SH-SY5Y cells, magnolol significantly attenuated MPP+-induced cytotoxicity and the production of reactive oxygen species. These results suggest that magnolol has protective effects via an antioxidative mechanism in bothin vivoandin vitromodels of Parkinson’s disease.

An Update on the Role of Nitric Oxide in the Neurodegenerative Processes of Parkinson's Disease

2016 ◽  
Vol 23 (24) ◽  
pp. 2666-2679 ◽  
Author(s):  
Félix Jiménez-Jiménez ◽  
Hortensia Alonso-Navarro ◽  
María Herrero ◽  
Elena García-Martín ◽  
José Agúndez
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease

Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease

2019 ◽  
Vol 26 (20) ◽  
pp. 3719-3753 ◽  
Author(s):  
Natasa Kustrimovic ◽  
Franca Marino ◽  
Marco Cosentino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Neurodegenerative Disorder ◽  
Neurodegenerative Process ◽  
Progressive Degeneration ◽  
Cytokine Levels ◽  
Inflammatory Phenotype ◽  
Immune Challenges

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
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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