scholarly journals Exploring the Therapeutic Potential of Protein Tyrosine Phosphatase 1B in hAPP-J20 Mouse Model of Alzheimer's Disease

2020 ◽  
Vol 40 (32) ◽  
pp. 6100-6102
Author(s):  
Judy Ghalayini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Protein Tyrosine Phosphatase ◽  
Therapeutic Potential ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Model Of Alzheimer’S Disease

scholarly journals Neuronal Protein Tyrosine Phosphatase 1B Hastens Amyloid β-Associated Alzheimer's Disease in Mice

2020 ◽  
Vol 40 (7) ◽  
pp. 1581-1593 ◽  
Author(s):  
Konrad M. Ricke ◽  
Shelly A. Cruz ◽  
Zhaohong Qin ◽  
Kaveh Farrokhi ◽  
Fariba Sharmin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Amyloid Β ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Neuronal Protein

scholarly journals STEP inhibition prevents Aβ-mediated damage in dendritic complexity and spine density in Alzheimer’s disease.

2020 ◽  
Author(s):  
Manavi Chatterjee ◽  
Jeemin Kwon ◽  
Jessie Benedict ◽  
Marija Kamceva ◽  
Pradeep Kurup ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mouse Model ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Spine Density ◽  
Protein Tyrosine ◽  
Dendritic Complexity ◽  
Ad Mouse Model

AbstractLoss of dendritic spines and decline of cognitive function are hallmarks of patients with Alzheimer’s disease (AD). Previous studies have shown that AD pathophysiology involves increased expression of a central nervous system-enriched protein tyrosine phosphatase called STEP (STriatal-Enriched protein tyrosine Phosphatase). STEP opposes the development of synaptic strengthening by dephosphorylating substrates, including GluN2B, Pyk2 and ERK1/2. Genetic reduction of STEP as well as pharmacological inhibition of STEP improves cognitive function and hippocampal memory in the 3xTg AD mouse model. Here, we show that the improved cognitive function is accompanied by an increase in synaptic connectivity in cell cultures as well as in the triple transgenic AD mouse model, further highlighting the potential of STEP inhibitors as a therapeutic agent.

scholarly journals Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR−/− mouse model of atherosclerosis

2017 ◽  
Vol 131 (20) ◽  
pp. 2489-2501 ◽  
Author(s):  
Dawn Thompson ◽  
Nicola Morrice ◽  
Louise Grant ◽  
 Samantha Le Sommer ◽  
Emma K. Lees ◽  
...  
Keyword(s):  
Mouse Model ◽  
Atherosclerotic Plaque ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Plaque Formation ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Cvd Risk ◽  
Protein Tyrosine ◽  
Atherosclerotic Plaque Formation

Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with type 1 or type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance, due to impaired insulin receptor (IR) signalling. Here, we demonstrate that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR prevents and reverses atherosclerotic plaque formation in an LDLR−/− mouse model of atherosclerosis. Acute (single dose) or chronic PTP1B inhibitor (trodusquemine) treatment of LDLR−/− mice decreased weight gain and adiposity, improved glucose homeostasis and attenuated atherosclerotic plaque formation. This was accompanied by a reduction in both, circulating total cholesterol and triglycerides, a decrease in aortic monocyte chemoattractant protein-1 (MCP-1) expression levels and hyperphosphorylation of aortic Akt/PKB and AMPKα. Our findings are the first to demonstrate that PTP1B inhibitors could be used in prevention and reversal of atherosclerosis development and reduction in CVD risk.

Reduced Insulin Resistance Contributes to the Beneficial Effect of Protein Tyrosine Phosphatase-1B Deletion in a Mouse Model of Sepsis

Shock ◽  
2017 ◽  
Vol 48 (3) ◽  
pp. 355-363 ◽  
Author(s):  
Eugénie Delile ◽  
Rémi Nevière ◽  
Pierre-Alain Thiébaut ◽  
Julie Maupoint ◽  
Paul Mulder ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mouse Model ◽  
Beneficial Effect ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine

scholarly journals The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer’s disease

2020 ◽  
Vol 117 (50) ◽  
pp. 32145-32154
Author(s):  
Niklas Lonnemann ◽  
Shirin Hosseini ◽  
Carlo Marchetti ◽  
Damaris B. Skouras ◽  
Davide Stefanoni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Potential ◽  
Active Form ◽  
Specific Inhibitor ◽  
Morris Water Maze Test ◽  
Model Of Alzheimer’S Disease

Numerous studies demonstrate that neuroinflammation is a key player in the progression of Alzheimer’s disease (AD). Interleukin (IL)-1β is a main inducer of inflammation and therefore a prime target for therapeutic options. The inactive IL-1β precursor requires processing by the the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome into a mature and active form. Studies have shown that IL-1β is up-regulated in brains of patients with AD, and that genetic inactivation of the NLRP3 inflammasome improves behavioral tests and synaptic plasticity phenotypes in a murine model of the disease. In the present study, we analyzed the effect of pharmacological inhibition of the NLRP3 inflammasome using dapansutrile (OLT1177), an oral NLRP3-specific inhibitor that is safe in humans. Six-month-old WT and APP/PS1 mice were fed with standard mouse chow or OLT1177-enriched chow for 3 mo. The Morris water maze test revealed an impaired learning and memory ability of 9-mo-old APP/PS1 mice (P = 0.001), which was completely rescued by OLT1177 fed to mice (P = 0.008 to untreated APP/PS1). Furthermore, our findings revealed that 3 mo of OLT1177 diet can rescue synaptic plasticity in this mouse model of AD (P = 0.007 to untreated APP/PS1). In addition, microglia were less activated (P = 0.07) and the number of plaques was reduced in the cortex (P = 0.03) following NLRP3 inhibition with OLT1177 administration. We also observed an OLT1177 dose-dependent normalization of plasma metabolic markers of AD to those of WT mice. This study suggests the therapeutic potential of treating neuroinflammation with an oral inhibitor of the NLRP3 inflammasome.

scholarly journals Administration of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI Improves Cognitive and Memory Function in the Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Hongwon Kim ◽  
Sumin Kim ◽  
Sang-jun Park ◽  
Gwoncheol Park ◽  
Hakdong Shin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Therapeutic Potential ◽  
Memory Function ◽  
Bifidobacterium Longum ◽  
Bifidobacterium Bifidum ◽  
Pathological Features ◽  
Bdnf Expression ◽  
Model Of Alzheimer’S Disease

Recent evidence indicates that gut microbiota could interact with the central nervous system and affect brain function, including cognition and memory. In this study, we investigated whether Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) alleviated the pathological features in a mouse model of Alzheimer’s disease (AD). Administration of B. bifidum BGN4 and B. longum BORI effectively suppressed amyloidosis and apoptotic processes and improved synaptic plasticity by ameliorating the neuroinflammatory response and BDNF expression. Moreover, behavioral tests indicated that B. bifidum BGN4 and B. longum BORI attenuated the cognitive and memory disability of AD mice. Taken together, the present study highlights the therapeutic potential of B. bifidum BGN4 and B. longum BORI for suppressing the pathological features of AD.

scholarly journals Protein tyrosine phosphatase 1B targets PITX1/p120RasGAP thus showing therapeutic potential in colorectal carcinoma

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hao-Wei Teng ◽  
Man-Hsin Hung ◽  
Li-Ju Chen ◽  
Mao-Ju Chang ◽  
Feng-Shu Hsieh ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Therapeutic Potential ◽  
Tyrosine Phosphatase ◽  
Tumor Model ◽  
Colon Carcinogenesis ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Potential Biomarker ◽  
The Stability

Abstract Protein tyrosine phosphatase 1B (PTP1B) is known to promote the pathogenesis of diabetes and obesity by negatively regulating insulin and leptin pathways, but its role associated with colon carcinogenesis is still under debate. In this study, we demonstrated the oncogenic role of PTP1B in promoting colon carcinogenesis and predicting worse clinical outcomes in CRC patients. By co-immunoprecipitation, we showed that PITX1 was a novel substrate of PTP1B. Through direct dephosphorylation at Y160, Y175 and Y179, PTP1B destabilized PITX1, which resulted in downregulation of the PITX1/p120RasGAP axis. Interestingly, we found that regorafenib, the approved target agent for advanced CRC patients, exerted a novel property against PTP1B. By inhibiting PTP1B activity, regorafenib treatment augmented the stability of PITX1 protein and upregulated the expression of p120RasGAP in CRC. Importantly, we found that this PTP1B-dependant PITX1/p120RasGAP axis determines the in vitro anti-CRC effects of regorafenib. The above-mentioned effects of regorafenib were confirmed by the HT-29 xenograft tumor model. In conclusion, we demonstrated a novel oncogenic mechanism of PTP1B on affecting PITX1/p120RasGAP in CRC. Regorafenib inhibited CRC survival through reserving PTP1B-dependant PITX1/p120RasGAP downregulation. PTP1B may be a potential biomarker predicting regorafenib effectiveness, and a potential solution for CRC.

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