Beclin1 decreases the RIPA-insoluble fraction of amyotrophic lateral sclerosis-linked SOD1 mutant via autophagy

Publication date: Available online 12 October 2018Source: Neuroscience LettersAuthor(s): Yan-Ming Wei, Bo HanAbstractMany neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), are characterised by the intracellular appearance of protein aggregates or insoluble materials. Accelerated removal of related toxic proteins might be beneficial for these diseases. Here we describe an inducible role of Beclin1, an essential regulator for autophagy, in degradation of the familial ALS-linked Cu/Zn superoxide dismutase 1 (SOD1) mutant. We confirmed that the SOD1 mutant exhibited an increased RIPA (radioimmune precipitation assay buffer, containing NP40 and sodium deoxycholate)-insolubility compared with SOD1 wild-type (WT). Also, the insoluble fraction formed by SOD1 mutant was greatly reduced by coexpressing Beclin1 in both neuronal and non-neuronal cell lines. Pharmacological inhibition of autophagy diminished the effect of Beclin1 and resulted in an accumulation of insoluble SOD1. Our results support the role of Beclin1 in the involvement of autophagic degradation of SOD1 mutant. We propose Beclin1 enhances autophagy and presents a possible therapeutic strategy for familial ALS.
Source: Neuroscience Letters - Category: Neuroscience Source Type: research

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Source: NYT Health - Category: Consumer Health News Authors: Tags: Stroke Brain Epilepsy Amyotrophic Lateral Sclerosis Emory University Georgia Institute of Technology Mayo Clinic Nature (Journal) University of California, Berkeley University of California, San Francisco Bauby, Jean-Dominique your-f Source Type: news
Publication date: Available online 23 April 2019Source: Seminars in Cell &Developmental BiologyAuthor(s): Cinzia Volonté, Susanna Amadio, Paola Fabbrizio, Savina ApolloniAbstractToday neuroscience is dominated by the perspective that microglia are essential elements in any integrated view of the nervous system. A number of different neuroinflammatory conditions affect the CNS where microglia involvement, and particularly microgliosis, is not only a prominent feature, but also a pathogenic key mechanism of disease. On the other side, microglia can also constitute an important trigger of neuronal protection during...
Source: Seminars in Cell and Developmental Biology - Category: Cytology Source Type: research
Publication date: 23 April 2019Source: Cell Reports, Volume 27, Issue 4Author(s): Brittany N. Flores, Xingli Li, Ahmed M. Malik, Jose Martinez, Asim A. Beg, Sami J. BarmadaSummaryThe majority of individuals with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit neuronal cytoplasmic inclusions rich in the RNA binding protein TDP43. Even so, the relation between the RNA binding properties of TDP43 and neurodegeneration remains obscure. Here, we show that engineered mutations disrupting a salt bridge between the RNA recognition motifs of TDP43 interfere with RNA binding and eliminate the recog...
Source: Cell Reports - Category: Cytology Source Type: research
Publication date: Available online 24 April 2019Source: Molecular and Cellular NeuroscienceAuthor(s): Maria Gomez, Doris GermainAbstractThe mitochondrial unfolded protein response (UPRmt) is rapidly gaining attention. While the CHOP (ATF4/5) axis of the UPRmt was the first to be described, other axes have subsequently been reported. Validation of this complex pathway in C. elegans has been extensively studied. However, validation of the UPRmt in mouse models of disease known to implicate mitochondrial reprogramming or dysfunction, such as cancer and neurodegeneration, respectively, is only beginning to emerge. This review ...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
This study was carried out in accordance with the recommendations of the National Animal Care and Use Committee of the University of Buenos Aires (CICUAL). The protocol was approved by the CICUAL. Mice were kept under a 12-h light/dark cycle, with controlled temperature (23 ± 2°C) and humidity (40–60%) and had ad libitum access to food and water. To produce hTDP-43 transgenic lines, as described previously (Igaz et al., 2011), pronucleus of fertilized eggs from C57BL/6J × C3HeJ F1 matings were injected with a vector containing hTDP-43-WT cDNA. Monogenic tetO-TDP-WT12 mice wer...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Zhong Luo Fused in sarcoma (FUS) is a DNA/RNA binding protein that is involved in RNA metabolism and DNA repair. Numerous reports have demonstrated by pathological and genetic analysis that FUS is associated with a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and polyglutamine diseases. Traditionally, the fibrillar aggregation of FUS was considered to be the cause of those diseases, especially via its prion-like domains (PrLDs), which are rich in glutamine and asparagine residues. Lately, a nonfibrillar self-assembling phenomenon, liquid...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Krisztina Banfai1,2, Kitti Garai1,2, David Ernszt2,3, Judit E. Pongracz1,2 and Krisztian Kvell1,2* 1Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pécs, Pécs, Hungary 2Szentagothai Research Center, University of Pécs, Pécs, Hungary 3Faculty of Medicine, Institute of Physiology, University of Pécs, Pécs, Hungary During senescence, Wnt4 expression is down-regulated (unlike their Frizzled receptors), while PPARgamma expression increases in the thymus. Together, these changes allow for thymic degeneration to occur, observed as adipose involut...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Physiology - Category: Physiology Source Type: research
Authors: Connors K, Mahony L, Morgan P Abstract BACKGROUND: Assistive devices enhance independence and quality of life for people living with motor neuron disease (MND), but prescription can be challenging. OBJECTIVE: Improved prescription of assistive devices, through improved understanding of the relationship between clinical phenotypes, Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) functional domain sub-scores and assistive technology required by people living with MND. METHODS: Prospective, observational consecutive-sample study of 269 patients with MND diagnosis. MAIN O...
Source: NeuroRehabilitation - Category: Rehabilitation Tags: NeuroRehabilitation Source Type: research
AbstractThe term proteostasis reflects the fine-tuned balance of cellular protein levels, mediated through a vast network of biochemical pathways. This requires the regulated control of protein folding, post-translational modification, and protein degradation. Due to the complex interactions and intersection of proteostasis pathways, exposure to stress conditions may lead to a disruption of the entire network. Incorrect protein folding and/or modifications during protein synthesis results in inactive or toxic proteins, which may overload degradation mechanisms. Further, a disruption of autophagy and the endoplasmic reticul...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
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