NLRP3 Inflammasome Activation in a Transgenic Amyotrophic Lateral Sclerosis Model

In conclusion, our results showed the activation of the NLRP3 inflammasome in the brain of SOD1G93A rats, indicating that inflammation plays a main role in ALS.
Source: Inflammation - Category: Allergy & Immunology Source Type: research

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Authors: Walker LC, Meadows MR, Du Y, March LK, Jones JK Abstract BACKGROUND: Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ∼47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treat...
Source: Restorative Neurology and Neuroscience - Category: Neurology Tags: Restor Neurol Neurosci Source Type: research
Publication date: 17 July 2018Source: Cell Reports, Volume 24, Issue 3Author(s): Elke Bogaert, Steven Boeynaems, Masato Kato, Lin Guo, Thomas R. Caulfield, Jolien Steyaert, Wendy Scheveneels, Nathalie Wilmans, Wanda Haeck, Nicole Hersmus, Joost Schymkowitz, Frederic Rousseau, James Shorter, Patrick Callaerts, Wim Robberecht, Philip Van Damme, Ludo Van Den BoschSummaryRNA-binding protein aggregation is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). To gain better insight into the molecular interactions underlying thi...
Source: Cell Reports - Category: Cytology Source Type: research
(VIB (the Flanders Institute for Biotechnology)) The mutated and aggregated protein FUS is implicated in two neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Using a newly developed fruit fly model, researchers led by prof. Ludo Van Den Bosch (VIB-KU Leuven) have zoomed in on the protein structure of FUS to gain more insight into how it causes neuronal toxicity and disease.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
A therapy for an inherited form of amyotrophic lateral sclerosis extends survival and reverses signs of neuromuscular damage in mice and rats, a new study shows.
Source: Health News - UPI.com - Category: Consumer Health News Source Type: news
Abnormalities in nucleic acid processing are associated with the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations inMatrin 3 (MATR3), a poorly understood DNA- and RNA-binding protein, cause familial ALS/FTD, and MATR3 pathology is a feature of sporadic disease, suggesting that MATR3 dysfunction is integrally linked to ALS pathogenesis. Using a rat primary neuron model to assess MATR3-mediated toxicity, we noted that neurons were bidirectionally vulnerable to MATR3 levels, with pathogenic MATR3 mutants displaying enhanced toxicity. MATR3 ’s zinc finger domains partially m...
Source: eLife - Category: Biomedical Science Tags: Cell Biology Neuroscience Source Type: research
Amyotrophic lateral sclerosis (ALS) is a complex disease that affects the nerve cells in your brain and spinal cord, which affects many parts of the body. The brain loses the ability to control muscles throughout the body, including the ability to speak, eat, move arms and legs, and eventually breathe. Because ALS affects the brain, some people also begin to have difficulties with their thinking and mood. The symptoms of ALS can affect everyone differently; and as a result, most people with ALS need treatment from many different types of medical care providers.
Source: Archives of Physical Medicine and Rehabilitation - Category: Rehabilitation Authors: Tags: Organization news Source Type: research
t S Abstract VCP/p97 (valosin containing protein) is a key regulator of cellular proteostasis. It orchestrates protein turnover and quality control in vivo, processes fundamental for proper cell function. In humans, mutations in VCP lead to severe myo- and neuro-degenerative disorders such as inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD), amyotrophic lateral sclerosis (ALS) or and hereditary spastic paraplegia (HSP). We analyzed here the in vivo role of Vcp and its novel interactor Washc4/Swip (WASH complex subunit 4) in the vertebrate model zebrafish (Danio rerio). We...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research
In this study, HCY was observed to sensitize the neuromuscular junction to ROS-induced depression of spontaneous transmission frequency, an effect we found to be mediated by a N-methyl-D-aspartate receptor (NMDAR) and nitric oxide (NO). The NMDAR antagonist D, L-2-amino-5-phosphonopentanoic acid prevented the HCY-induced sensitization to oxidative stress. Disrupting NO activity with either the nitric oxide synthase I antagonist Nω-nitro-L-arginine methyl ester hydrochloride or the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide potassium salt also prevented sensitization. Moreover, rep...
Source: NeuroReport - Category: Neurology Tags: Cellular, Molecular and Developmental Neuroscience Source Type: research
This article discusses the preclinical pharmacology, pharmacokinetics, safety profile, clinical studies and drug interactions of edaravone (Radicava) in ALS. PMID: 29998226 [PubMed - in process]
Source: Drugs of Today - Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of a disease spectrum with shared clinical, genetic and pathological features. These include near ubiquitous pathological inclusions of the RNA binding protein (RBP) TDP-43, and often the presence of a GGGGCC expansion in theC9ORF72 (C9) gene. Previously we reported that the sequestration of hnRNP H altered the splicing of target transcripts in C9ALS patients (Conlon et al. 2016). Here we show that this signature also occurs in half of 50 post-mortem sporadic, non-C9 ALS/FTD brains. Furthermore, and equally surprisingly, these 'like-C9...
Source: eLife - Category: Biomedical Science Tags: Biochemistry and Chemical Biology Human Biology and Medicine Source Type: research
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