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Condition: ALS

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Total 36 results found since Jan 2013.

Repetitive elements in aging and neurodegeneration
Trends Genet. 2023 Mar 17:S0168-9525(23)00034-3. doi: 10.1016/j.tig.2023.02.008. Online ahead of print.ABSTRACTRepetitive elements (REs), such as transposable elements (TEs) and satellites, comprise much of the genome. Here, we review how TEs and (peri)centromeric satellite DNA may contribute to aging and neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Alterations in RE expression, retrotransposition, and chromatin microenvironment may shorten lifespan, elicit neurodegeneration, and impair memory and movement. REs may cause these phenotypes via DNA damage, protein sequestration, insertional muta...
Source: Trends in Genetics : TIG - March 19, 2023 Category: Genetics & Stem Cells Authors: Katie E Copley James Shorter Source Type: research

G βγ signaling regulates microtubule-dependent control of Golgi integrity
In this study, we use siRNA against Gβ1/2 or specific Gγ subunits to deplete their expression, and show that their knockdown causes a significant reduction in nocodazole-induced Golgi fragmentation. We establish that knockdown of Gβγ or inhibition of Gβγ with gallein resulted in decreased activation of protein kinase D (PKD) in response to nocodazole treatment. We demonstrate that restricting the amount of free Gβγ available for signaling by either inhibiting Gαi activation using pertussis toxin or by knockdown of the non-GPCR GEF, Girdin/GIV protein, results in a substantial decrease in nocodazole-induced Golgi f...
Source: Cellular Signalling - February 22, 2023 Category: Cytology Authors: Kalpana Rajanala Philip B Wedegaertner Source Type: research

A candidate protective factor in amyotrophic lateral sclerosis: heterogenous nuclear ribonucleoprotein G
In this study, we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis. Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting, and cell proliferation and proteins (TAR DNA binding protein 43, superoxide dismutase 1, and Bax) were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells. We analyzed heterogen...
Source: Cell Research - December 26, 2022 Category: Cytology Authors: Fang Yang Wen-Zhi Chen Shi-Shi Jiang Xiao-Hua Wang Ren-Shi Xu 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

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

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

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

Genome-wide siRNA screening reveals that DCAF4-mediated ubiquitination of optineurin stimulates autophagic degradation of Cu,Zn-superoxide dismutase Cell Biology
Cu, Zn superoxide dismutase (SOD1) is one of the genes implicated in the devastating neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Although the precise mechanisms of SOD1 mutant (SOD1mut)-induced motoneuron toxicity are still unclear, defects in SOD1 proteostasis are known to have a critical role in ALS pathogenesis. We previously reported that the SOD1mut adopts a conformation that exposes a Derlin-1–binding region (DBR) and that DBR-exposed SOD1 interacts with Derlin-1, leading to motoneuron death. We also found that an environmental change, i.e. zinc depletion, induces a conformational change in WT S...
Source: Journal of Biological Chemistry - March 5, 2020 Category: Chemistry Authors: Kengo Homma, Hiromitsu Takahashi, Naomi Tsuburaya, Isao Naguro, Takao Fujisawa, Hidenori Ichijo Tags: Molecular Bases of Disease 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

TDP-43 knockdown causes innate immune activation via protein kinase R in astrocytes.
Abstract TAR-DNA binding protein 43 (TDP-43) is a multifunctional RNA binding protein directly implicated in the etiology of amyotrophic lateral sclerosis (ALS). Previous studies have demonstrated that loss of TDP-43 function leads to intracellular accumulation of non-coding repetitive element transcripts and double-stranded RNA (dsRNA). These events could cause immune activation and contribute to the neuroinflammation observed in ALS, but this possibility has not been investigated. Here, we knock down TDP-43 in primary rat astrocytes via siRNA, and we use RNA-seq, immunofluorescence, and immunoblotting to show th...
Source: Neurobiology of Disease - June 19, 2019 Category: Neurology Authors: LaRocca TJ, Mariani A, Watkins LR, Link CD Tags: Neurobiol Dis Source Type: research