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The aetiology of sporadic amyotrophic lateral sclerosis (ALS), a fatal paralytic disease, is largely unknown. Here we show that there is a defect in the editing of the messenger RNA encoding the GluR2 subunit of glutamate AMPA receptors in the spinal motor neurons of individuals affected by ALS. This failure to swap an arginine for a glutamine residue at a(More)
In human brain, developmental up-regulation in RNA editing at the Q/R site was evident in GluR5 and GluR6, but GluR2 editing in the white matter was down-regulated. Each ADAR mRNA expression was up-regulated in the gray matter, whereas differently regulated in the white matter. ADAR2 mRNA was not overexpressed in the brains of Down's syndrome subjects, nor(More)
Compelling evidence supports contributions of glutamate receptor overactivation ('excitotoxicity') to neurodegeneration in both acute conditions, such as stroke, and chronic neurodegenerative conditions, such as amyotrophic lateral sclerosis. However, anti-excitotoxic therapeutic trials, which have generally targeted highly Ca2+ permeable NMDA-type(More)
Enhancement of calcium influx through the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor is a plausible mechanism underlying selective neuronal death in amyotrophic lateral sclerosis (ALS). The calcium conductance of the AMPA receptor is regulated by the GluR2 subunit that is edited at the glutamine/arginine residue site in the(More)
Both the appearance of cytoplasmic inclusions containing phosphorylated TAR DNA-binding protein (TDP-43) and inefficient RNA editing at the GluR2 Q/R site are molecular abnormalities observed specifically in motor neurons of patients with sporadic amyotrophic lateral sclerosis (ALS). The purpose of this study is to determine whether a link exists between(More)
The ionotropic glutamate receptor (GluR) subunits GluR2, GluR5 and GluR6 are subject to RNA editing at their Q/R sites, resulting in significant alterations in the channel properties of the receptors. RNA editing at the Q/R site of GluRs is both developmentally and regionally regulated. Here we provide the first quantitative measurements of both mRNAs of(More)
It has been repeatedly reported that spinal motor neurons are selectively vulnerable to AMPA receptor-mediated excitotoxicity. Therefore, identifying the uniqueness of AMPA receptors that are expressed on motor neurons, especially in individuals affected with sporadic amyotrophic lateral sclerosis (ALS) is essential for elucidating the etiology of this(More)
OBJECTIVE To assess corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS) by correlating diffusion tensor imaging (DTI) measures with intra- and extracranial central motor conduction time (CMCT) and clinical features of the patients. METHODS We investigated 31 patients with ALS and 31 normal volunteers by DTI and measured(More)
The vestibular nerves are known to influence neuronal circuits in the medullary cardiovascular areas and, through the cerebellar vermis, the basal ganglia and the limbic system. By means of noisy galvanic vestibular stimulation (GVS), it might be possible to ameliorate blunted responsiveness of degenerated neuronal circuits of patients with multi system(More)
Glutamate transporters play a pivotal role in terminating glutamatergic transmission by eliminating glutamate from the synaptic cleft. Four different glutamate transporter cDNAs have been isolated thus far, and their tissue distribution has been investigated using northern blot and immunohistochemical analysis. We raised site-directed antisera against a(More)