scholarly journals HOTTIP downregulation reduces neuronal damage and microglial activation in Parkinson's disease cell and mouse models

2022 ◽  
Vol 17 (4) ◽  
pp. 887
Author(s):  
Peng Sun ◽  
Peng Lun ◽  
Tao Ji ◽  
De-Hong Wan ◽  
Xia Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Models ◽  
Microglial Activation ◽  
Neuronal Damage ◽  
Disease Cell

Novel LRRK2 GTP-binding inhibitors reduced degeneration in Parkinson's disease cell and mouse models

2014 ◽  
Vol 23 (23) ◽  
pp. 6212-6222 ◽  
Author(s):  
T. Li ◽  
D. Yang ◽  
S. Zhong ◽  
J. M. Thomas ◽  
F. Xue ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Models ◽  
Gtp Binding ◽  
Disease Cell ◽  
Binding Inhibitors

scholarly journals The association of enteric neuropathy with gut phenotypes in acute and progressive models of Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rachel M. McQuade ◽  
Lewis M. Singleton ◽  
Hongyi Wu ◽  
Sophie Lee ◽  
Remy Constable ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Models ◽  
Nuclear Translocation ◽  
Neuronal Damage ◽  
Intracerebral Injection ◽  
Neuronal Marker ◽  
Enteric Neuropathy ◽  
Soma Size ◽  
Oxide Synthase

AbstractParkinson’s disease (PD) is associated with neuronal damage in the brain and gut. This work compares changes in the enteric nervous system (ENS) of commonly used mouse models of PD that exhibit central neuropathy and a gut phenotype. Enteric neuropathy was assessed in five mouse models: peripheral injection of MPTP; intracerebral injection of 6-OHDA; oral rotenone; and mice transgenic for A53T variant human α-synuclein with and without rotenone. Changes in the ENS of the colon were quantified using pan-neuronal marker, Hu, and neuronal nitric oxide synthase (nNOS) and were correlated with GI function. MPTP had no effect on the number of Hu+ neurons but was associated with an increase in Hu+ nuclear translocation (P < 0.04). 6-OHDA lesioned mice had significantly fewer Hu+ neurons/ganglion (P < 0.02) and a reduced proportion of nNOS+ neurons in colon (P < 0.001). A53T mice had significantly fewer Hu+ neurons/area (P < 0.001) and exhibited larger soma size (P < 0.03). Treatment with rotenone reduced the number of Hu+ cells/mm2 in WT mice (P < 0.006) and increased the proportion of Hu+ translocated cells in both WT (P < 0.02) and A53T mice (P < 0.04). All PD models exhibited a degree of enteric neuropathy, the extent and type of damage to the ENS, however, was dependent on the model.

scholarly journals Development of an α-synuclein knockdown peptide and evaluation of its efficacy in Parkinson’s disease models

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jack Wuyang Jin ◽  
Xuelai Fan ◽  
Esther del Cid-Pellitero ◽  
Xing-Xing Liu ◽  
Limin Zhou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Microglial Activation ◽  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Motor Impairment ◽  
Convincing Evidence ◽  
Disease Models ◽  
Potential Use

AbstractConvincing evidence supports the premise that reducing α-synuclein levels may be an effective therapy for Parkinson’s disease (PD); however, there has been lack of a clinically applicable α-synuclein reducing therapeutic strategy. This study was undertaken to develop a blood-brain barrier and plasma membrane-permeable α-synuclein knockdown peptide, Tat-βsyn-degron, that may have therapeutic potential. The peptide effectively reduced the level of α-synuclein via proteasomal degradation both in cell cultures and in animals. Tat-βsyn-degron decreased α-synuclein aggregates and microglial activation in an α-synuclein pre-formed fibril model of spreading synucleinopathy in transgenic mice overexpressing human A53T α-synuclein. Moreover, Tat-βsyn-degron reduced α-synuclein levels and significantly decreased the parkinsonian toxin-induced neuronal damage and motor impairment in a mouse toxicity model of PD. These results show the promising efficacy of Tat-βsyn-degron in two different animal models of PD and suggest its potential use as an effective PD therapeutic that directly targets the disease-causing process.

Systematic Investigation of Mouse Models of Parkinson’s Disease by Transcriptome Mapping on a Brain-Specific Genome-Scale Metabolic Network

2021 ◽  
Author(s):  
Ecehan Abdik ◽  
Tunahan Cakir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Metabolic Network ◽  
Mouse Models ◽  
Mus Musculus ◽  
Metabolic Networks ◽  
Systematic Investigation ◽  
Omics Data ◽  
Metabolic Alterations ◽  
Genome Scale

Genome-scale metabolic networks enable systemic investigation of metabolic alterations caused by diseases by providing interpretation of omics data. Although Mus musculus (mouse) is one of the most commonly used model...

scholarly journals α-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation

2015 ◽  
Vol 112 (15) ◽  
pp. E1926-E1935 ◽  
Author(s):  
Shijun Wang ◽  
Chun-Hsien Chu ◽  
Tessandra Stewart ◽  
Carmen Ginghina ◽  
Yifei Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Migration ◽  
Neuronal Damage ◽  
Directional Migration ◽  
Chronic Neuroinflammation ◽  
Tyrosine Protein Kinase ◽  
Microglial Migration ◽  
Directional Cell Migration ◽  
Cytoskeleton Rearrangement

Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson’s disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-syn aggregates act as chemoattractants to direct microglia toward damaged neurons. In addition, we describe a mechanism underlying this directional migration of microglia. Specifically, chemotaxis occurs when α-syn binds to integrin CD11b, leading to H2O2 production by NADPH oxidase. H2O2 directly attracts microglia via a process in which extracellularly generated H2O2 diffuses into the cytoplasm and tyrosine protein kinase Lyn, phosphorylates the F-actin–associated protein cortactin after sensing changes in the microglial intracellular concentration of H2O2. Finally, phosphorylated cortactin mediates actin cytoskeleton rearrangement and facilitates directional cell migration. These findings have significant implications, given that α-syn–mediated microglial migration reaches beyond Parkinson’s disease.

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