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Genomes and GenesSpecies | R H BrownSummaryAffiliation: Harvard University Country: USA Publications
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Amyotrophic lateral sclerosis. Insights from geneticsR H Brown
Day Neuromuscular Research Laboratory, Massachusetts General Hospital East, Charlestown, USA
Arch Neurol 54:1246-50. 1997..In the United States, it is estimated that there are 20,000 to 30,000 cases. About 10% of cases are inherited as an autosomal dominant trait; familial and sporadic ALS are clinically indistinguishable...
A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALSA M Wills
Cecil B Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, MA 02129, USA
Neurology 73:16-24. 2009..However, several other large studies, including five genome-wide association studies, have not duplicated this finding...
Paraoxonase 1 (PON1) organophosphate hydrolysis is not reduced in ALSA M Wills
Day Neuromuscular Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Neurology 70:929-34. 2008..We tested the hypothesis that this association correlates with functional changes in paraoxonase 1 (PON1, MIM 168820)...- Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosisT J Kwiatkowski
Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
Science 323:1205-8. 2009..Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders... - Caspase-1 and -3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosisP Pasinelli
Massachusetts General Hospital East, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 97:13901-6. 2000..Thus, a common toxicity of mutant SOD1 is a sequential activation of at least two caspases, caspase-1 that acts slowly as a chronic initiator and caspase-3 acting as the final effector of cell death... - New VAPB deletion variant and exclusion of VAPB mutations in familial ALSJ E Landers
Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital East, Charlestown, MA, USA
Neurology 70:1179-85. 2008..No additional mutations have been identified... - Enhancement of diphtheria toxin potency by replacement of the receptor binding domain with tetanus toxin C-fragment: a potential vector for delivering heterologous proteins to neuronsJ W Francis
Cecil B Day Center for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
J Neurochem 74:2528-36. 2000..These results suggest that a catalytically inactive form of DAB(389)TTC may be useful as a nonviral vehicle to deliver exogenous proteins to the cytosolic compartment of neurons... - The pharmacokinetics and pharmaco-dynamics of Procysteine in amyotrophic lateral sclerosisM E Cudkowicz
Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown 02114, USA
Neurology 52:1492-4. 1999..We found that oral administration of Procysteine was safe. Procysteine enters CSF after both IV and oral dosing and accumulates to significant levels in CSF. We also observed that CSF levels of glutathione fall dramatically with aging... - SOD1A4V-mediated ALS: absence of a closely linked modifier gene and origination in AsiaW J Broom
Day Neuromuscular Research Laboratory, Massachusetts General Hospital, 114 16th Street, Navy Yard, Charlestown, MA 02129, USA
Neurosci Lett 430:241-5. 2008..The conserved minimal haplotype is statistically more similar to Asian than European population DNA sets, suggesting that the A4V mutation arose in native Asian-Americans who reached the Americas through the Bering Strait... - Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacityD Trotti
Membrane Biology Program, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 276:576-82. 2001..The resulting alteration in glutamate clearance capacity likely contributes to excitotoxicity that participates in motor neuron degeneration in amyotrophic lateral sclerosis... - Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron diseaseM Nagai
Department of Neuroscience, Division of Neurology, Institute for Experimental Animals, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
J Neurosci 21:9246-54. 2001..g., direct administration of viral- and cell-mediated therapies)... - A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementiaM Morita
Day Neuromuscular Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
Neurology 66:839-44. 2006..00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb. CONCLUSIONS: A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD... - Disease course unaltered by a single intracisternal injection of BMP-7 in ALS miceJ E Dreibelbis
Muscle Nerve 25:122-3. 2002 - Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase activityM E Cudkowicz
Day Neuromuscular Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
Neurology 59:729-34. 2002..To test this hypothesis, the authors generated transgenic ALS mice with altered levels of glutathione peroxidase (GSHPx), the major soluble enzyme that detoxifies H2O2... - Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidateA L McCormick
Centre for Virology, Department of Infection, University College London, London, UK
Neurology 70:278-83. 2008..We therefore developed a quantitative assay to study RT levels in ALS and examined the possibility that the recently discovered human gammaretrovirus XMRV (xenotropic MuLV-related virus) might be the source of the RT activity... - The proapoptotic BCL-2 family member BIM mediates motoneuron loss in a model of amyotrophic lateral sclerosisC Hetz
Cell Death Differ 14:1386-9. 2007 - A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosisM E Cudkowicz
Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Neurology 61:456-64. 2003..To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS... - Identification of potential CSF biomarkers in ALSG M Pasinetti
Geriatric Research, Education, and Clinical Center, Bronx Veterans Affairs Medical Center, Bronx, NY, USA
Neurology 66:1218-22. 2006..The clinical diagnosis of ALS is based entirely on clinical features. Identification of biomarkers for ALS would be important for diagnosis and might also provide clues to pathogenesis... - Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS miceA M Clement
Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
Science 302:113-7. 2003..Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons... - Failure to detect enterovirus in the spinal cord of ALS patients using a sensitive RT-PCR methodW A Nix
Respiratory and Enteric Viruses Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Neurology 62:1372-7. 2004..CONCLUSION: The reported association between EV infection and ALS was not confirmed by testing this set of specimens with these sensitive methods... - Detection of serum reverse transcriptase activity in patients with ALS and unaffected blood relativesA J Steele
Centre of Virology, epartment of Infection, University College London, UK
Neurology 64:454-8. 2005..The finding of a similarly increased prevalence in blood relatives of ALS patients raises the possibility that the observed RT activity might be due to an inherited endogenous retrovirus... - ABCD1 translation-initiator mutation demonstrates genotype-phenotype correlation for AMNM Aoki
Cecil B. Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Boston, MA, USA
Neurology 57:1956-62. 2001..Possible models for action of this truncated ALDP and full disease penetrance in heterozygotes are reviewed... - A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2S Hadano
NeuroGenes, International Cooperative Research Project, Japan
Nat Genet 29:166-73. 2001..Deletion mutations are predicted to cause a loss of protein function, providing strong evidence that ALS2 is the causative gene underlying this form of ALS... - Identification of three novel mutations in the gene for Cu/Zn superoxide dismutase in patients with familial amyotrophic lateral sclerosisP C Sapp
Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA
Neuromuscul Disord 5:353-7. 1995..These three mutations bring to 29 the total number of distinct SOD1 mutations associated with familial ALS... - Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible candidate genes for autosomal recessive familial amyotrophic lateral sclerosisR Berger
Eleanor Roosevelt Institute, Denver, Colorado 80206, USA
Somat Cell Mol Genet 21:121-31. 1995..Neither of these XDH genes appears to be highly expressed in human spinal cord. This evidence suggests that AO may be a candidate gene for FALS-AR... - Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosisA Pramatarova
Centre for Research in Neuroscience, McGill University, Montreal
Am J Hum Genet 56:592-6. 1995..These two mutations reduce significantly SOD 1 enzyme activity in lymphoblasts. Our results suggest that SOD 1 mutations are responsible for > or = 13% of FALS cases... - Amyotrophic lateral sclerosis: recent insights from genetics and transgenic miceR H Brown
Cecil B. Day Laboratory for Neuromuscular Research Neurology Service, Massachusetts General Hospital, Boston 02114
Cell 80:687-92. 1995 - Identification of two novel mutations and a new polymorphism in the gene for Cu/Zn superoxide dismutase in patients with amyotrophic lateral sclerosisJ Esteban
Cecil B. Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129
Hum Mol Genet 3:997-8. 1994 - Chromosomal localization of glutamate receptor genes: relationship to familial amyotrophic lateral sclerosis and other neurological disorders of mice and humansP Gregor
Molecular Neurobiology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224
Proc Natl Acad Sci U S A 90:3053-7. 1993.... - Three novel mutations and two variants in the gene for Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosisB A Hosler
Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA
Neuromuscul Disord 6:361-6. 1996..An individual with an apparently sporadic case of ALS carries a three base pair deletion in exon 5 of the SOD1 gene. These three mutations bring to 38 the total number of distinct SOD1 mutations associated with familial ALS... - Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosisM Aoki
Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA
Ann Neurol 43:645-53. 1998..These studies indicate that germline mutations in the EAAT2 gene are infrequent and do not explain the presence of variant mRNA transcripts of EAAT2 in more than one-half of ALS cases... - Gating of the L-type Ca channel in human skeletal myotubes: an activation defect caused by the hypokalemic periodic paralysis mutation R528HJ A Morrill
Program in Neuroscience, Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts 02214, USA
J Neurosci 18:10320-34. 1998..The R528H mutation had no effect on the kinetics or voltage dependence of inactivation... - Dysferlin is a surface membrane-associated protein that is absent in Miyoshi myopathyC Matsuda
Day Neuromuscular Research Laboratory, Massachusetts General Hospital East, Charlestown 02129, USA
Neurology 53:1119-22. 1999..Although it is not essential for initial myogenesis, it appears to be critical for sustained normal function in mature muscle... - Novel mutations in the gene encoding ATP-binding cassette 1 in four tangier disease kindredsM E Brousseau
Lipid Metabolism Laboratory, JM USDA Human Nutrition Research Center on Aging at Tufts University and Department of Medicine, New England Medical Center, Boston, MA 02111, USA
J Lipid Res 41:433-41. 2000..These results establish a causal role for mutations in hABC-1 in TD and indicate that this transporter has a critical function in the regulation of intracellular lipid trafficking that dramatically affects plasma HDL cholesterol levels... - Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22B A Hosler
Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, MGH East, Bldg 149, 13th St, Charlestown, MA 02129, USA
JAMA 284:1664-9. 2000..An understanding of the genetic bases of combined disorders, such as amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD), will likely provide insight into mechanisms of these and related neurodegenerative diseases... - Amyotrophic lateral sclerosis: pathogenesisR H Brown
Department of Neurology, University of Leuven School of Medicine, University Hospital Gasthuisberg, Belgium
Semin Neurol 21:131-9. 2001..Ultimately, it is hoped that insights from these types of studies will improve the prospects for developing meaningful therapies of ALS... - A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysisC V Rojas
Department of Molecular Genetics, University of Pittsburgh School of Medicine, Pennsylvania 15261
Nature 354:387-9. 1991..This same change was found in a sporadic case of HYPP as a new mutation. We have therefore discovered a voltage-gated channel mutation responsible for a human genetic disease...