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Condition: ALS

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Total 36 results found since Jan 2013.

LOF and GOF Mechanisms of TDP-43 Proteinopathies Neurobiology
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U) are two clinically distinct neurodegenerative conditions sharing a similar histopathology characterized by the nuclear clearance of TDP-43 and its associated deposition into cytoplasmic inclusions in different areas of the central nervous system. Given the concomitant occurrence of TDP-43 nuclear depletion and cytoplasmic accumulation, it has been proposed that TDP-43 proteinopathies originate from either a loss-of-function (LOF) mechanism, a gain-of-function (GOF) process, or both. We have addressed this i...
Source: Journal of Biological Chemistry - September 8, 2016 Category: Chemistry Authors: Cascella, R., Capitini, C., Fani, G., Dobson, C. M., Cecchi, C., Chiti, F. Tags: Molecular Bases of Disease Source Type: research

GSE83484 RNA sequencing of human fibroblasts after SUPT4H1 siRNA treatment
Contributors : Nicholas J Kramer ; Aaron D Gitler ; Julien CouthouisSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAsses the transcriptome-wide changes associated with depletion of transcription elongation factor, SUPT4H1, in human fibroblasts. An expanded hexanucleotide repeat in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). Therapeutics (e.g., antisense oligonucleotides) are being developed to target RNAs containing the expanded repeat sequence (GGGGCC); however, this approach is complicated by the presence of ant...
Source: GEO: Gene Expression Omnibus - September 9, 2016 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

Protective roles of SLC30A3 against endoplasmic reticulum stress via ERK1/2 activation.
In conclusion, this study suggested that SLC30A3 is supposed to play a protective role against ER stress, which is related to ERK1/2 activation. PMID: 27678294 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - September 23, 2016 Category: Biochemistry Authors: Kurita H, Okuda R, Yokoo K, Inden M, Hozumi I Tags: Biochem Biophys Res Commun Source Type: research

Quantification of the Relative Contributions of Loss-of-function and Gain-of-function Mechanisms in TAR DNA-binding Protein 43 (TDP-43) Proteinopathies Neurobiology
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U) are two clinically distinct neurodegenerative conditions sharing a similar histopathology characterized by the nuclear clearance of TDP-43 and its associated deposition into cytoplasmic inclusions in different areas of the central nervous system. Given the concomitant occurrence of TDP-43 nuclear depletion and cytoplasmic accumulation, it has been proposed that TDP-43 proteinopathies originate from either a loss-of-function (LOF) mechanism, a gain-of-function (GOF) process, or both. We have addressed this i...
Source: Journal of Biological Chemistry - September 8, 2016 Category: Chemistry Authors: Roberta Cascella, Claudia Capitini, Giulia Fani, Christopher M. Dobson, Cristina Cecchi, Fabrizio Chiti Tags: Molecular Bases of Disease Source Type: research

Silencing strategies for therapy of SOD1-mediated ALS
Publication date: 1 January 2017 Source:Neuroscience Letters, Volume 636 Author(s): Brigitte van Zundert, Robert H. Brown Amyotrophic lateral sclerosis (ALS) is an adult-onset, lethal, paralytic disorder caused by the degeneration of motor neurons. Our understanding of this disease has been greatly facilitated by studies of familial ALS caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Evidence indicates that misfolded wild-type SOD1 may also be pathogenic in sporadic ALS. Mutant SOD1 is neurotoxic through multiple mechanisms. Because the pathogenicity of mutant SOD1 is proportional to the dose of th...
Source: Neuroscience Letters - December 5, 2016 Category: Neuroscience Source Type: research

Retrotransposon activation contributes to neurodegeneration in a < i > Drosophila < /i > TDP-43 model of ALS
We report that such expression of hTDP-43 impairs small interfering RNA (siRNA) silencing, which is the major post-transcriptional mechanism of retrotransposable element (RTE) control in somatic tissue. This is accompanied by de-repression of a panel of both LINE and LTR families of RTEs, with somewhat different elements being active in response to hTDP-43 expression in glia versus neurons. hTDP-43 expression in glia causes an early and severe loss of control of a specific RTE, the endogenous retrovirus (ERV)gypsy. We demonstrate thatgypsy causes the degenerative phenotypes in these flies because we are able to rescue the ...
Source: PLoS Genetics - March 15, 2017 Category: Genetics & Stem Cells Authors: Lisa Krug Source Type: research

DDX3 binding with CK1 ε was closely related to motor neuron degeneration of ALS by affecting neurite outgrowth.
In this study, we first investigated the expression of DDX3 and CK1ε in the spinal cord of SOD1-G93A ALS transgenic mice using RT-PCR, Western blot and immunohistochemical technique. Results showed that the altered expression of DDX3 and CK1ε was found in the spinal cord of ALS mice. DDX3 and CK1ε positive cells were mainly distributed in the anterior horn of spinal cord and co-localized with neurons not with glial cells, suggesting that the altered expression of DDX3 and CK1ε was closely related to motor neuron degeneration of ALS. Moreover, we selected NSC34 cell line and transfected pEGFP-G93A-SOD1 plasmid to furthe...
Source: American Journal of Translational Research - November 10, 2017 Category: Research Tags: Am J Transl Res Source Type: research

Resveratrol treatment reduces the vulnerability of SH-SY5Y cells and cortical neurons overexpressing SOD1-G93A to Thimerosal toxicity through SIRT1/DREAM/PDYN pathway.
Abstract In humans, mutation of glycine 93 to alanine of Cu++/Zn++ superoxide dismutase type-1 (SOD1-G93 A) has been associated to some familial cases of Amyotrophic Lateral Sclerosis (ALS). Several evidence proposed the involvement of environmental pollutants that like mercury could accelerate ALS symptoms. SH-SY5Y cells stably transfected with SOD1 and G93 A mutant of SOD1 constructs were exposed to non-toxic concentrations (0.01 µM) of ethylmercury thiosalicylate (thimerosal) for 24 hours. Interestingly, we found that thimerosal, in SOD1-G93 A cells, but not in SOD1 cells, reduced cell survival. Furthe...
Source: Neurotoxicology - November 29, 2018 Category: Neurology Authors: Laudati G, Mascolo L, Guida N, Sirabella R, Pizzorusso V, Bruzzaniti S, Serani A, Di Renzo G, Canzoniero LM, Formisano L Tags: Neurotoxicology Source Type: research

GSE135611 TDP-43 knockdown in primary rat astrocytes
Contributor : Thomas LaRoccaSeries Type : Expression profiling by high throughput sequencingOrganism : Rattus norvegicusTDP-43 is an RNA binding protein involved in amyotrophic lateral sclerosis and other neurodegenerative diseases. The purpose of this study was to determine if loss of TDP-43 function leads to accumulation of repetitive element transcripts, double-stranded RNA (dsRNA) and innate immune activation that may be involved in disease pathology. TDP-43 was knocked down in primary rat astrocytes via siRNA, cells were treated with/without ATP (an immune modulator), and polyA RNA-seq was performed to profile gene ex...
Source: GEO: Gene Expression Omnibus - August 9, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Rattus norvegicus Source Type: research

Decrease in ADAR1 expression by exposure to cigarette smoke enhances susceptibility to oxidative stress.
In conclusion, we show that ADAR1 expression is decreased by cigarette smoking and is a factor that contributes to the enhanced intracellular oxidative stress caused by cigarette smoking. PMID: 32439581 [PubMed - as supplied by publisher]
Source: Toxicology Letters - May 17, 2020 Category: Toxicology Authors: Takizawa M, Nakano M, Fukami T, Nakajima M Tags: Toxicol Lett Source Type: research

HuD regulates SOD1 expression during oxidative stress in differentiated neuroblastoma cells and sporadic ALS motor cortex.
Abstract The neuronal RNA-binding protein (RBP) HuD plays an important role in brain development, synaptic plasticity and neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's (AD). Bioinformatics analysis of the human SOD1 mRNA 3' untranslated region (3'UTR) demonstrated the presence of HuD binding adenine-uridine (AU)-rich instability-conferring elements (AREs). Using differentiated SH-SY5Y cells along with brain tissues from sporadic amyotrophic lateral sclerosis (sALS) patients, we assessed HuD-dependent regulation of SOD1 mRNA. In vitro binding and mRNA decay assays demonstrate that HuD specific...
Source: Neurobiology of Disease - November 30, 2020 Category: Neurology Authors: Michela D, Valentina S, Gardiner Amy S, Orietta P, Matteo B, Perrone-Bizzozero Nora I, Cristina C Tags: Neurobiol Dis Source Type: research

hTBK1-c.978T > A mutation promotes the ferroptosis in NSC-34 cells via mediation of KEAP1/NRF2/p62 signaling.
CONCLUSION: hTBK1-c.978T>A mutation promoted promotes the ferroptosis in NSC-34 cells via regulation of KEAP1/NRF2/p62 signaling. Thus, hTBK1-c.978T>A mutation may serve as a possible target for the treatment of ALS. PMID: 33312375 [PubMed]
Source: American Journal of Translational Research - December 15, 2020 Category: Research Tags: Am J Transl Res Source Type: research

Towards personalized medicine for amyotrophic lateral sclerosis
Trends Endocrinol Metab. 2021 Jul 26:S1043-2760(21)00155-7. doi: 10.1016/j.tem.2021.07.002. Online ahead of print.ABSTRACTMohassel et al. provide unprecedented dichotomy of consequences on sphingolipid biosynthesis between pathogenic variants in the SPTLC1 gene, responsible for either amyotrophic lateral sclerosis (ALS) or hereditary sensory and autonomic neuropathy type 1 (HSAN1). Normalization of sphingolipid levels by siRNA selectively targeting the ALS mutant allele mRNA sheds light on new therapeutic approaches.PMID:34325980 | DOI:10.1016/j.tem.2021.07.002
Source: Trends in Endocrinology and Metabolism: TEM - July 30, 2021 Category: Endocrinology Authors: Julien Cassereau Philippe Corcia Pascal Reynier Source Type: research