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Stress proteins located in the cytosol or endoplasmic reticulum (ER) maintain cell homeostasis and afford tolerance to severe insults. In neurodegenerative diseases, several chaperones ameliorate the accumulation of misfolded proteins triggered by oxidative or nitrosative stress, or of mutated gene products. Although severe ER stress can induce apoptosis,(More)
Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in Japan (incidence is 0.7-1.2 per 10,000 births), is characterized by congenital muscular dystrophy associated with brain malformation (micropolygria) due to a defect in the migration of neurons. We previously mapped the FCMD gene to a region of less(More)
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant, neurodegenerative disorder that affects the cerebellum and other areas of the central nervous system. We have devised a novel strategy, the direct identification of repeat expansion and cloning technique (DIRECT), which allows selective detection of expanded CAG repeats and cloning of the genes(More)
Mating-type (MAT) loci were cloned from two asexual (mitosporic) phytopathogenic ascomycetes, Fusarium oxysporum (a pyrenomycete) and Alternaria alternata (a loculoascomycete), by a polymerase chain reaction (PCR)-based strategy. The conserved high mobility group (HMG) box domain found in the MAT1-2-1 protein was used as a starting point for cloning and(More)
Hereditary progressive dystonia with marked diurnal fluctuation (HPD) (also known as dopa responsive dystonia) is a dystonia with onset in childhood that shows a marked response without any side effects to levodopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q. Here we report that GTP cyclohydrolase I is mapped to(More)
Conditions that perturb the function of the endoplasmic reticulum (ER) lead to an accumulation of proteins and subsequent induction of several responses, such as an increased expression of ER-resident chaperones involved in protein folding and activation of c-jun N-terminal kinase (JNK). These responses are mediated by a transmembrane kinase/ribonuclease,(More)
Sodium 4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid that has been used for treatment of urea cycle disorders in children, sickle cell disease, and thalassemia. It has been demonstrated recently that 4-PBA can act as a chemical chaperone by reducing the load of mutant or mislocated proteins retained in the endoplasmic reticulum (ER) under(More)
Alzheimer's disease (AD) is characterized by the accumulation of fibrillar amyloid-beta (Abeta) peptides to form amyloid plaques. Understanding the balance of production and clearance of Abeta peptides is the key to elucidating amyloid plaque homeostasis. Microglia in the brain, associated with senile plaques, are likely to play a major role in maintaining(More)
Mammalian cells acquire tolerance against multiple stressors through the high-level expression of stress-responsible genes. We have previously demonstrated that protein-disulfide isomerase (PDI) together with ubiquilin are up-regulated in response to hypoxia/brain ischemia, and play critical roles in resistance to these damages. We show here that ubiquilin(More)
The origins of reflected light changes associated with neuronal activity (optical signals) were investigated in rat somatosensory cortex with optical imaging, microspectrophotometry, and laser-Doppler flowmetry, and dynamic changes in local hemoglobin concentration and oxygenation were focused on. Functional activation was carried out by 2-second, 5-Hz(More)