Pur-alpha regulates cytoplasmic stress granule dynamics and ameliorates FUS toxicity

Abstract Amyotrophic lateral sclerosis is characterized by progressive loss of motor neurons in the brain and spinal cord. Mutations in several genes, including FUS, TDP43, Matrin 3, hnRNPA2 and other RNA-binding proteins, have been linked to ALS pathology. Recently, Pur-alpha, a DNA/RNA-binding protein was found to bind to C9orf72 repeat expansions and could possibly play a role in the pathogenesis of ALS. When overexpressed, Pur-alpha mitigates toxicities associated with Fragile X tumor ataxia syndrome (FXTAS) and C9orf72 repeat expansion diseases in Drosophila and mammalian cell culture models. However, the function of Pur-alpha in regulating ALS pathogenesis has not been fully understood. We identified Pur-alpha as a novel component of cytoplasmic stress granules (SGs) in ALS patient cells carrying disease-causing mutations in FUS. When cells were challenged with stress, we observed that Pur-alpha co-localized with mutant FUS in ALS patient cells and became trapped in constitutive SGs. We also found that FUS physically interacted with Pur-alpha in mammalian neuronal cells. Interestingly, shRNA-mediated knock down of endogenous Pur-alpha significantly reduced formation of cytoplasmic stress granules in mammalian cells suggesting that Pur-alpha is essential for the formation of SGs. Furthermore, ectopic expression of Pur-alpha blocked cytoplasmic mislocalization of mutant FUS and strongly suppressed toxicity associated with mutant FUS expression in primary motor ne...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Last month, House Speaker Nancy Pelosi unveiled aradical drug pricing plan, H.R. 3, that could jeopardize the development of innovative treatments for some of the most challenging diseases and leave U.S. patients behind. For example,researchers are focused every day on finding new treatments and cures for amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig ’s Disease), but Pelosi’s plan could threaten future treatments for ALS by imposing government-set prices on critical medicines, creating increased uncertainty and eroding incentives for investment into risky research and development (R&D).
Source: The Catalyst - Category: Pharmaceuticals Authors: Tags: Research and Development ALS Source Type: news
ConclusionsBoth classical opioid receptors and TLR4 participate in morphine-induced suppression of NK cell cytotoxic activity. These studies have important implications for maintenance of immune function during management of cancer pain.
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
ConclusionBBD could prevent and cure hepatic encephalopathy derived from both chronic and acute liver diseases. Here, we found that except for the direct improvement of blood and brain ammonia level, inflammation is likely an important target of BBD to treat hepatic encephalopathy. The anti-inflammatory role of BBD may lie in its regulation of the TLR4/MyD88/NF-κ B pathways.Graphical abstractBBD can prevent and cure hepatic encephalopathy derived from both chronic and acute liver diseases. BBD can reduce hyperammonemia as well as the systematic and neurological inflammation. Inflammation is likely an important target...
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
You're reading The ONE Secret Trick to Kill Negative Thinking Immediately, originally posted on Pick the Brain | Motivation and Self Improvement. If you're enjoying this, please visit our site for more inspirational articles. Do you ever have those bad days where your thoughts are just so negative all day long, everything feels like it’s too much for one person to handle. You obsessively question every decision you’ve ever made in your life, every small thing that has happened to you and basically just indulge in negative thinking to the point where you cry yourself asleep at night?   Don’t ...
Source: PickTheBrain | Motivation and Self Improvement - Category: Consumer Health News Authors: Tags: featured happiness psychology self improvement how to get rid of negative thoughts Overcoming negative thoughts positive self talk positive thinking positivity Source Type: blogs
We describe here a case of 48 y.o. male patient with ALK-positive NSCLC who was clinically managed for 6.5 years from the diagnosis. The tumor was surgically resected, but 8 months later multiple brain metastases were discovered. The patient started receiving platinum-based chemotherapy and then was enrolled in a clinical trial of second-generation ALK inhibitor ceritinib, which resulted in a 21 months stabilization. Following disease relapse, the patient was successfully managed for 33 months with different lines of chemo- and local ablative therapies. Chemotherapy regimens, including off-label combination of crizotinib +...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: In this study, a risk signature with five pseudogenes was constructed and shown to accurately predict 1-, 3-, and 5-year survival for glioma patient. The risk signature may serve as a potential target against glioma.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Glioma is the most malignant brain tumors in the world, the function and molecular mechanism of microRNA-199a (miR-199a) in glioma is not fully understood. Our research aims to investigate miR-199a/K-RAS axis in regulation of glioma tumor growth and chemoresistance. The function of miR-199a in glioma was investigated through in vitro and in vivo assays. We found that miR-199a in tumor tissues of glioma patients was significantly downregulated in this study. Kinase suppressor of ras 1 (K-RAS), was indicated as a direct target of miR-199a, as well as expression levels of K-RAS were inversely correlated with expression levels...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Smoking cessation is critical for reducing the risk of respiratory, cardiovascular diseases and cancers. However, most cessation attempts resulted in failure. In the present study, we aim to explore whether alterations of brain gray matter (GM) volume and functional connectivity (FC) are related to cessation outcomes, in hope of providing evidence for improving smoking cessation outcomes. Seventy-three smokers and 41 non-smokers were enrolled in the present study. All smokers participated in a 12-week smoking cessation treatment during which Varenicline was used to aid cessation. At the end of treatment, the smokers were d...
Source: Frontiers in Human Neuroscience - Category: Neuroscience Source Type: research
AbstractGlioblastoma (GBM) is the most aggressive intracranial tumors. Despite the comprehensive treatments, the median survival of GBM patients is still dismal. Consequently, it is critical to explore potential biomarkers and underlying molecular mechanisms of GBM. We integrated two datasets (GSE19728 and GSE 4290) to identify differentially expressed genes (DEGs) of GBM. Eighty-two GBM samples and 31 brain normal samples were screened by using GEO2R and Draw Venn Diagram. We carried out Database for Annotation, Visualization and Integrated Discovery (DAVID) to analyze gene ontology (GO) and Kyoto Encyclopedia of Genes an...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
Albert Sanfeliu1, Karsten Hokamp2, Michael Gill1 and Daniela Tropea1,3*1Neuropsychiatric Genetics, Department of Psychiatry, School of Medicine, Trinity Translational Medicine Institute, St James Hospital, Dublin, Ireland2Department of Genetics, School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland3Department of Psychiatry, School of Medicine, Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, IrelandRett syndrome is a rare neuropsychiatric disorder with a wide symptomatology including impaired communication and movement, cardio-respiratory abno...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
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