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Amyotrophic Lateral Sclerosis - PubMed

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Last Updated: 27 June 2022

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Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by the absence of motor neurons. Both TDP-43 and FUS have been implicated in RNA processing processes, such as microRNA biogenesis, transcription, and splicing. We find that miR-139 downregulation leads to the activation of canonical WNT signaling, as well as the discovery that the WNT transcriptional mediator u03b2-catenin is a key cause of MN degeneration in ALS. Our findings reveal the importance of homeostatic RNA networks in ALS.

Source link: https://doi.org/10.1016/j.stemcr.2022.05.019


Retromer dysfunction in amyotrophic lateral sclerosis.

Here, we report a decrease in the retromer proteins-vacuolar protein sorting 35, VPS26A, and VPS29-in patients with amyotrophic lateral sclerosis and in the ALS model produced by transgenic mice expressing the mutant superoxide dismutase-1 G93A. In Tg SOD1G93A mice, a viral vector expressing VPS35 contributes to the retromer deficit. Conversely, lowering the Vps35 levels in Tg SOD1G93A mice improves the disease phenotype.

Source link: https://doi.org/10.1073/pnas.2118755119


Integrated multi-omic data analysis and validation with yeast model show oxidative phosphorylation modulates protein aggregation in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis is a progressive, incurable amyloid aggregating neurodegenerative disease affecting the motor neurons. Our review of ALS patient datasets revealed deregulation in Non-alcoholic fatty acid liver disease and oxidative phosphorylation. In addition, a network analysis of mitochondrial electron transport chain showed enrichment of proteins and protein-drug interaction network analysis of mitochondrial Complex III and IV. Ramaswamy H. Sarma's report brought together our results show a vital role for mitochondrial oxidative phosphorylation in amyloid formation and as a potential therapeutic target in ALS.

Source link: https://doi.org/10.1080/07391102.2022.2090441


A pathologically confirmed case of combined amyotrophic lateral sclerosis with C9orf72 mutation and multiple system atrophy.

A substantial proportion of cases of amyotrophic lateral sclerosis and frontotemporal lobar degeneration has been observed in C9orf72. There have been no reported pathologically confirmed cases of ALS with C9orf72 mutation and multiple system atrophy as far as we are aware. We describe a man who appeared with extrapyramidal signs, including cogwheel rigidity, and was, subsequently, diagnosed with Parkinson's disease or parkinsonian syndrome. Subsequent testing six months later revealed further abnormal upper and lower motor neuron signs, raising the likelihood of ALS. The macroscopic and microscopic examination of the brain and spinal cord revealed ALS pathology with neuronal dysfunction, particularly in the anterior horns of the cord and the motor cortex. This is the first reported case of pathologically confirmed combined ALS-C9orf72 and MSA.

Source link: https://doi.org/10.1111/neup.12808


Metabolic Profile and Pathological Alterations in the Muscle of Patients with Early-Stage Amyotrophic Lateral Sclerosis.

We established the metabolome of muscle and serum of ALS patients and compared their findings with the clinical status and pathological changes present in the muscle. A distinct serum metabolome for ALS was found by metabolomics analysis that compared to controls, revealing an excellent discriminant profile for muscle metabolome. Muscle teignation issues were attributed to a lack of Forced Vital Capacity. SOD3 and GLRX2 upregulation in ALS muscle was demonstrated by Transcriptomics review of key antioxidant enzymes. ALS revealed more complicated II/CS and lower LDH levels in ALS than controls, according to an analysis of mitochondrial enzymatic activity in muscle.

Source link: https://doi.org/10.3390/biomedicines10061307


Transplantation of Human Glial Progenitors to Immunodeficient Neonatal Mice with Amyotrophic Lateral Sclerosis (SOD1/rag2).

Amyotrophic lateral sclerosis is a progressive, lethal disease with no effective treatment. ALS' neurodegenerative morphology was an attractive target for stem cell-based regenerative therapies. Both preclinical and clinical settings have been transplanted, but no convincing results have been reported. Human glial confined precursors transplanted intraventricularly to neonatal, immunodeficient mice extended the life of dysmyelinated mice by dysmyelinated mice. In the mouse model of ALS, intraspinal injection of hGRPs also provided benefits. We have recently developed an immunodeficient model of ALS, as well as testing the procedure used in dysmyelinated mice of intraventricular transplantation of hGRPs to immunodeficient mice in this research. Grafting in neonatal immunodeficient recipients did not prevent ALS-related cell death, which could account for the lack of positive therapeutic effects. In the clinic, we encourage stem cell and ALS groups to develop and use cell tracking technologies to help identify cell fates.

Source link: https://doi.org/10.3390/antiox11061050


Granulocyte-colony stimulating factor (G-CSF): an emerging therapeutic approach for amyotrophic lateral sclerosis (ALS).

Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by neuronal degeneration and inflammation in the nerves. In mSOD1G93A mouse models, preliminary clinical results have demonstrated significant safety of G-CSF therapy. However, clinical trials on ALS patients failed to replicate pre-clinical findings. This research sought to comprehensively examine the clinical and pre-clinical evidence addressing G-CSF in ALS therapy, considering the potential role of G-CSF in nervous system repair.

Source link: https://doi.org/10.1007/s13760-022-01996-z


Imaging Neurodegenerative Metabolism in Amyotrophic Lateral Sclerosis with Hyperpolarized [1-13C]pyruvate MRI.

The cause of amyotrophic lateral sclerosis is still unclear, causing early detection of the disease and timely treatment is lacking. The pathology of ALS seems to involve specific changes in carbohydrate metabolism, which can be diagnostic or therapeutic goals. [1-13C]pyruvate-to-[1-13C]lactate exchange shows a lateralized change in the [1-13C]pyruvate-to-[1-13C]lactate exchange, with no changes in the exchange from [1-13C]pyruvate to 13C-bicarbonate, according to We found a lateralized difference in [1-13C]pyruvate-to-[1-13C]carbonate exchange from [1-13C]pyruvate]pyruvate-to-[1-13C]bi pyruvate exchange from [1-13C]pyruvate-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to-to The patient's symptoms and presentation with elevated-motor neuron affection and cortical hyperexcitability corresponded with the patient's [1-13C]pyruvate-to-[1-13C] lactate exchange, which corresponded with the patient's signs and presentation with upper-motor neuron affection and cortical hyperexcitability. The results presented here show that performing hyperpolarized MRI in ALS is definitely feasible.

Source link: https://doi.org/10.3390/tomography8030129


Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis.

We isolated white matter from the motor cortex of ALS patients and age- and sex-matched controls, carried out targeted lipidomic measurements, qPCR for relevant lipid metabolizing enzymes, and Western blotting for myelin proteins from myelin proteins from ALS patients and age-matched controls. Although myelin protein composition was similar in ALS and control tissue, both the lipid levels and expression of their corresponding enzymes were dysregulated, underlining a probable increase in myelin composition as well as a possible change in myelin composition.

Source link: https://doi.org/10.3390/metabo12060554


Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4.

Amyotrophic lateral sclerosis is a heterogenous neurodegenerative disease that affects motor neurons and voluntary muscle control1. Although several ALS-related genes have been shown to influence immune functions2, it is unclear if specific immune factors account for ALS heterogeneity. Patients with ALS4 begin experiencing motor problems by the time they are in their teens, and the majority of them need devices to aid with walking by their fifties. We describe an immunological signature that includes clonally expanded, terminally differentiated effector memory CD8 cells in the central nervous system and mice that carry the ALS4-causative L389S mutation. In knock-in mice, increased frequencies of antigen-specific CD8 T cells reveal motor neuron disease progression and correlation with anti-glioma antibodies, which are correlated with immunity to motor neuron disease and autophagy. In patients with ALS4-like fibroblasts, clonally increased TEMRA CD8 T cells circulate in the peripheral blood.

Source link: https://doi.org/10.1038/s41586-022-04844-5

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions