High-Throughput LC–MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development

Chronic pain is highly prevalent worldwide and severely affects daily lives of patients and family members. Praeruptorin C (Pra-C) is a main active ingredient derived from Peucedanum praeruptorum Dunn, traditionally used as antibechic, anti-bronchitis and anti-hypertension drug. Here, we evaluated the effects of Pra-C in a chronic inflammatory pain mouse model induced by complete Freund’s adjuvant (CFA) injection. Pra-C (3 mg/kg) treatment for just 3 days after CFA challenge relieved CFA-induced mechanical allodynia and hindpaw edema in mice. In the anterior cingulate cortex (ACC), Pra-C treatment inhibited microglia activation and reduced levels of proinflammatory cytokines, TNF-α and IL-1β, and suppressed upregulation of glutamate receptors caused by CFA injection. In addition, Pra-C attenuated neuronal hyperexcitability in ACC of CFA-injected mice. In vitro studies confirmed the analgesic effect of Pra-C was due to its inhibitory ability on microglial activation. In conclusion, Pra-C administration had a certain effect on relieving chronic pain by inhibiting microglial activation, attenuating proinflammatory cytokine releasing and regulating excitatory synaptic proteins in the ACC of the CFA-injected mice.

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Mice carrying an analogous heterozygous dynamin 2 K562E mutation that causes neuropathy in humans develop predominant characteristics of a primary myopathy

Human Molecular Genetics ◽

10.1093/hmg/ddaa034 ◽

2020 ◽

Vol 29 (8) ◽

pp. 1253-1273

Author(s):

Jorge A Pereira ◽

Joanne Gerber ◽

Monica Ghidinelli ◽

Daniel Gerber ◽

Luigi Tortola ◽

...

Keyword(s):

Mouse Model ◽

Treatment Strategies ◽

Underlying Disease ◽

Potential Treatment ◽

Type B ◽

Disease Mechanism ◽

Demyelinating Neuropathy ◽

Charcot Marie Tooth ◽

Dynamin 2

Abstract Some mutations affecting dynamin 2 (DNM2) can cause dominantly inherited Charcot–Marie–Tooth (CMT) neuropathy. Here, we describe the analysis of mice carrying the DNM2 K562E mutation which has been associated with dominant-intermediate CMT type B (CMTDIB). Contrary to our expectations, heterozygous DNM2 K562E mutant mice did not develop definitive signs of an axonal or demyelinating neuropathy. Rather, we found a primary myopathy-like phenotype in these mice. A likely interpretation of these results is that the lack of a neuropathy in this mouse model has allowed the unmasking of a primary myopathy due to the DNM2 K562E mutation which might be overshadowed by the neuropathy in humans. Consequently, we hypothesize that a primary myopathy may also contribute to the disease mechanism in some CMTDIB patients. We propose that these findings should be considered in the evaluation of patients, the determination of the underlying disease processes and the development of tailored potential treatment strategies.

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Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation

The FASEB Journal ◽

10.1096/fj.02-0799fje ◽

2003 ◽

Vol 17 (8) ◽

pp. 1-18 ◽

Cited By ~ 102

Author(s):

Mario Delgado ◽

Doina Ganea

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Vasoactive Intestinal Peptide ◽

Microglial Activation ◽

Neuroprotective Effect

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High-throughput proteomic analysis of human infiltrating ductal carcinoma of the breast

PROTEOMICS ◽

10.1002/pmic.200300560 ◽

2003 ◽

Vol 3 (10) ◽

pp. 1863-1873 ◽

Cited By ~ 118

Author(s):

Richard I. Somiari ◽

Anthony Sullivan ◽

Stephen Russell ◽

Stella Somiari ◽

Hai Hu ◽

...

Keyword(s):

High Throughput ◽

Proteomic Analysis ◽

Ductal Carcinoma ◽

Carcinoma Of The Breast ◽

Infiltrating Ductal Carcinoma

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Slowing disease progression in the SOD1 mouse model of ALS by blocking neuregulin-induced microglial activation

Neurobiology of Disease ◽

10.1016/j.nbd.2017.12.012 ◽

2018 ◽

Vol 111 ◽

pp. 118-126 ◽

Cited By ~ 9

Author(s):

Jianguo Liu ◽

Elise Allender ◽

Jiajing Wang ◽

Eleanor H. Simpson ◽

Jeffrey A. Loeb ◽

...

Keyword(s):

Mouse Model ◽

Disease Progression ◽

Microglial Activation ◽

Sod1 Mouse

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PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22041882 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1882

Author(s):

Abdelrahman M. Elsayed ◽

Emine Bayraktar ◽

Paola Amero ◽

Salama A. Salama ◽

Abdelaziz H. Abdelaziz ◽

...

Keyword(s):

Mouse Model ◽

Long Noncoding Rna ◽

Proteomic Analysis ◽

Noncoding Rna ◽

Mtor Pathway ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Physical Interaction ◽

Cisplatin Sensitivity

Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpression of PRKAR1B-AS2 is negatively correlated with overall survival in OC patients. Furthermore, PRKAR1B-AS2 knockdown-attenuated proliferation, migration, and invasion of OC cells and ameliorated cisplatin and alpelisib resistance in vitro. In proteomic analysis, silencing PRKAR1B-AS2 markedly inhibited protein expression of PI3K-110α and abrogated the phosphorylation of PDK1, AKT, and mTOR, with no significant effect on PTEN. The RNA immunoprecipitation detected a physical interaction between PRKAR1B-AS2 and PI3K-110α. Moreover, PRKAR1B-AS2 knockdown by systemic administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with PRKAR1B-AS2–specific small interfering RNA enhanced cisplatin sensitivity in a xenograft OC mouse model. In conclusion, PRKAR1B-AS2 promotes tumor growth and confers chemoresistance by modulating the PI3K/AKT/mTOR pathway. Thus, targeting PRKAR1B-AS2 may represent a novel therapeutic approach for the treatment of OC patients.

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