scholarly journals Riluzole Selective Antioxidant Effects in Cell Models Expressing Amyotrophic Lateral Sclerosis Endophenotypes

2019 ◽  
Vol 17 (3) ◽  
pp. 438-442 ◽  
Author(s):  
Gessica Sala ◽  
Alessandro Arosio ◽  
Elisa Conti ◽  
Simone Beretta ◽  
Christian Lunetta ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cell Models ◽  
Antioxidant Effects ◽  
Lateral Sclerosis

scholarly journals Nucleolin Rescues TDP-43 Toxicity in Yeast and Human Cell Models

2021 ◽  
Vol 15 ◽  
Author(s):  
Caterina Peggion ◽  
Maria Lina Massimino ◽  
Roberto Stella ◽  
Raissa Bortolotto ◽  
Jessica Agostini ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cell Viability ◽  
Human Cell ◽  
Neurodegenerative Disorders ◽  
Nuclear Protein ◽  
Human Cells ◽  
Cell Models ◽  
Nuclear Retention ◽  
Beneficial Effects ◽  
Lateral Sclerosis

TDP-43 is a nuclear protein involved in pivotal processes, extensively studied for its implication in neurodegenerative disorders. TDP-43 cytosolic inclusions are a common neuropathologic hallmark in amyotrophic lateral sclerosis (ALS) and related diseases, and it is now established that TDP-43 misfolding and aggregation play a key role in their etiopathology. TDP-43 neurotoxic mechanisms are not yet clarified, but the identification of proteins able to modulate TDP-43-mediated damage may be promising therapeutic targets for TDP-43 proteinopathies. Here we show by the use of refined yeast models that the nucleolar protein nucleolin (NCL) acts as a potent suppressor of TDP-43 toxicity, restoring cell viability. We provide evidence that NCL co-expression is able to alleviate TDP-43-induced damage also in human cells, further supporting its beneficial effects in a more consistent pathophysiological context. Presented data suggest that NCL could promote TDP-43 nuclear retention, reducing the formation of toxic cytosolic TDP-43 inclusions.

γ-Oryzanol mitigates oxidative stress and prevents mutant SOD1-Related neurotoxicity in Drosophila and cell models of amyotrophic lateral sclerosis

2019 ◽  
Vol 160 ◽  
pp. 107777 ◽  
Author(s):  
Chunting Zhang ◽  
Weiwei Liang ◽  
Hongyong Wang ◽  
Yueqing Yang ◽  
Tianhang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Cell Models ◽  
Mutant Sod1 ◽  
Lateral Sclerosis

Human stem cell models of neurodegeneration: From basic science of amyotrophic lateral sclerosis to clinical translation

2022 ◽  
Vol 29 (1) ◽  
pp. 11-35
Author(s):  
Elisa Giacomelli ◽  
Björn F. Vahsen ◽  
Elizabeth L. Calder ◽  
Yinyan Xu ◽  
Jakub Scaber ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Stem Cell ◽  
Basic Science ◽  
Clinical Translation ◽  
Human Stem Cell ◽  
Cell Models ◽  
Stem Cell Models ◽  
Lateral Sclerosis

scholarly journals The C9ORF72 Gene, Implicated in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia, Encodes a Protein That Functions in Control of Endothelin and Glutamate Signaling

2018 ◽  
Vol 38 (22) ◽  
Author(s):  
Vitalay Fomin ◽  
Patricia Richard ◽  
Mainul Hoque ◽  
Cynthia Li ◽  
Zhuoying Gu ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Frontotemporal Dementia ◽  
Morphological Changes ◽  
Cell Models ◽  
Glutamate Signaling ◽  
Protein Levels ◽  
Rna Analysis ◽  
C9orf72 Gene ◽  
Lateral Sclerosis

ABSTRACT A GGGGCC repeat expansion in the C9ORF72 (C9) gene is the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Several mechanisms have been proposed to account for its toxicity, including the possibility that reduced C9 protein levels contribute to disease. To investigate this possibility, we examined the effects of reduced C9 levels in several cell systems. We first showed that C9 knockdown (KD) in U87 glioblastoma cells results in striking morphological changes, including vacuolization and alterations in cell size. Unexpectedly, RNA analysis revealed changes in expression of many genes, including genes involved in endothelin (EDN) signaling and immune system pathways and multiple glutamate cycling genes (e.g., EAAT2), which were verified in several cell models, including astrocytes and brain samples from C9-positive patients. Consistent with deregulation of the glutamate cycling genes, elevated intracellular glutamate was detected in both KD cells and patient astrocytes. Importantly, levels of mRNAs encoding EDN1 and its receptors, known to be elevated in ALS, were sharply increased by C9 KD, likely resulting from an observed activation of NF-κB signaling and/or a possible role of a C9 isoform in gene control.

Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 63 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Panying Rong
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Acoustic Analysis ◽  
Speaking Rate ◽  
Disease Stage ◽  
Healthy Controls ◽  
Tongue Movement ◽  
Major Barrier ◽  
Syllable Repetition ◽  
Oral Diadochokinesis ◽  
Lateral Sclerosis

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

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