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Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1-/- mice showed cell-autonomous microglial(More)
The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in(More)
OBJECTIVE In familial amyotrophic lateral sclerosis (fALS) harboring superoxide dismutase (SOD1) mutations (fALS1), SOD1 toxicity has been linked to its propensity to misfold and aggregate. It has recently been proposed that misfolded SOD1 may be causative of all types of ALS, including sporadic cases (sALS). In the present study, we have used a specific(More)
The multisubunit Golgi-associated retrograde protein (GARP) complex is required for tethering and fusion of endosome-derived transport vesicles to the trans-Golgi network. Mutation of leucine-967 to glutamine in the Vps54 subunit of GARP is responsible for spinal muscular atrophy in the wobbler mouse, an animal model of amyotrophic lateral sclerosis. The(More)
We performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course (relapsing with at least partial remissions or secondary progressive disease). Lesions were segmented on the conventional proton density and T2-weighted magnetic resonance images, and(More)
Mislocalization of the TAR-DNA binding protein (TDP-43) from the nucleus to the cytoplasm of diseased motor neurons and association with intraneuronal ubiquitinated inclusions has recently been reported in amyotrophic lateral sclerosis (ALS). Here, we have investigated TDP-43 immunoreactivity in three lines of mutant SOD1 transgenic mice, G93A, G37R and(More)
BACKGROUND Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS. METHODS A total of 330 patients from 20 medical centers were randomized(More)
OBJECTIVE To determine the effects of resistance exercise on function, fatigue, and quality of life in individuals with ALS. METHODS Subjects with a diagnosis of clinically definite, probable, or laboratory-supported ALS, forced vital capacity (FVC) of 90% predicted or greater, and an ALS Functional Rating Scale (ALSFRS) score of 30 or greater were(More)
MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more(More)
OBJECTIVE Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative(More)