Genomes and Genes
Peter St George Hyslop
Affiliation: University of Toronto
- Structural biology of presenilin 1 complexesYi Li
Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Addenbrookes Hospital, Hills Road, Cambridge CB2 0XY, UK
Mol Neurodegener 9:59. 2014..An increasingly detailed understanding of the structural biology of the presenilin complex is an essential step towards rational design of substrate- and/or cleavage site-specific modulators of presenilin complex function. ..
- ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanismTetsuro Murakami
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
Hum Mol Genet 21:1-9. 2012..Our data suggest that FUS mutants cause neuronal dysfunction by a dominant gain-of-function effect related either to neurotoxic aggregates of mutant FUS in the cytoplasm or to dysfunction in its RNA-binding functions...
- Role of p73 in Alzheimer disease: lack of association in mouse models or in human cohortsBadri Vardarajan
Department of Medicine Biomedical Genetics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA
Mol Neurodegener 8:10. 2013..Here, we reevaluated tau pathologies in the same TgCRND8 mouse model as the previous studies...
- The isotropic fractionator provides evidence for differential loss of hippocampal neurons in two mouse models of Alzheimer's diseaseHannah Brautigam
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Mol Neurodegener 7:58. 2012..We investigated whether two APP mouse models characterized by different folding states of amyloid showed different neuronal densities using an accurate method of cell counting...
- Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer riskKarolien Bettens
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, 2610 Antwerpen, Belgium
Mol Neurodegener 7:3. 2012....
- Assembly of the presenilin γ-/ε-secretase complexP St George-Hyslop
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
J Neurochem 120:84-8. 2012..Because the structure and assembly of these complexes underlies their activity, this review will discuss current work on the assembly of the complex and on presenilin-interacting proteins that regulate secretase activity...
- Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivoJohn W Steele
Departments of Neurology, Psychiatry and Alzheimer s Disease Research Center, Mount Sinai School of Medicine, New York, NY, 10029, USA
Mol Neurodegener 4:51. 2009..In the current study, we assessed the effect of acute dosing of latrepirdine on levels of extracellular Abeta using in vitro and in vivo experimental systems...
- Dietary composition modulates brain mass and solubilizable Abeta levels in a mouse model of aggressive Alzheimer's amyloid pathologySteve Pedrini
Farber Institute for the Neurosciences, Jefferson Medical College, Philadelphia PA USA
Mol Neurodegener 4:40. 2009..abstract:..
- Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTDParastoo Momeni
Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, MD, USA
BMC Neurol 6:44. 2006..A new locus for amyotrophic lateral sclerosis--frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p...
- Molecular biology and genetics of Alzheimer's diseasePeter H St George-Hyslop
Department of Medicine, Division of Neurology, The Toronto Hospital, University of Toronto, 6, Queen s Park Crescent West, Toronto, Ontario, Canada
C R Biol 328:119-30. 2005..Knowledge of this biochemical cascade now provides several potential targets for the development of diagnostics and therapeutics...
- Genetic factors in the genesis of Alzheimer's diseaseP H St George-Hyslop
Department of Medicine Division of Neurology, University Health Network, University of Toronto, Toronto, Ontario, Canada M5S 3H2
Ann N Y Acad Sci 924:1-7. 2000..Some of the genes are highly penetrant (PS1, PS2, beta APP); the other, APOE, is a weaker susceptibility factor. Several additional genes are suspected to exist but have not yet been cloned...
- The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-cateninG Yu
Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Medical Biophysics, University of Toronto, Toronto, Ontario M5S 3H2, Canada
J Biol Chem 273:16470-5. 1998....
- Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's diseaseR Sherrington
Department of Medicine Neurology, University of Toronto, Ontario, Canada
Nature 375:754-60. 1995..Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3...
- Nicastrin binds to membrane-tethered NotchF Chen
Centre for Research in Neurodegenerative Diseases Departments of Medicine and Medical Biophysics, University of Toronto, Tanz Neuroscience Building, 6 Queen s Park Crescent West, Toronto, Ontario M5S 3H2, Canada
Nat Cell Biol 3:751-4. 2001..In addition, we report that the Notch and betaAPP pathways do not significantly compete with each other...
- Biology of presenilins as causative molecules for Alzheimer diseaseM Nishimura
Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Ontario, Canada
Clin Genet 55:219-25. 1999..Furthermore, presenilins interact with beta-catenin to form presenilin complexes and presenilin mutations effect beta-catenin signalling pathways...
- Identification of the genetic locus for keratosis palmaris et plantaris on chromosome 17 near the RARA and keratin type I genesE I Rogaev
Department of Medicine, University of Toronto, Ontario, Canada
Nat Genet 5:158-62. 1993..Our analysis provide a region which should be investigated for contiguous gene syndromes in such pedigrees...
- Absence of linkage between familial amyotrophic lateral sclerosis and copper chaperone for the superoxide dismutase gene locus in two Italian pedigreesA Orlacchio
Centre for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, University of Toronto, 6 Queen s Park Crescent West, Toronto, Ontario, Canada
Neurosci Lett 285:83-6. 2000..Diagnoses were made using the El Escorial criteria. The results of our study provide no evidence of a linkage between markers flanking the CCS gene and familial amyotrophic lateral sclerosis (FALS) in these FALS kindreds...
- PS1 Alzheimer's disease family with spastic paraplegia: the search for a gene modifierE Rogaeva
Centre for Research in Neurodegenerative Diseases, University of Toronto, and Department of Medicine Division of Neurology, Ontario, Canada
Neurology 61:1005-7. 2003..The authors have excluded that this modifier effect originates from coding sequence variations in three SP genes or from a second mutation in the other AD genes...
- Inhibiting amyloid precursor protein C-terminal cleavage promotes an interaction with presenilin 1G Verdile
Sir James McCusker Alzheimer s Disease Research Unit and Department of Surgery, University of Western Australia, Hollywood Private Hospital, Nedlands, Western Australia 6009
J Biol Chem 275:20794-8. 2000..These findings suggest that PS1 may mediate the shuttling of APP fragments and/or facilitate their presentation for gamma-secretase cleavage through a direct interaction...
- Aberrant splicing in the presenilin-1 intron 4 mutation causes presenile Alzheimer's disease by increased Abeta42 secretionC De Jonghe
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, Laboratory of Molecular Genetics, Born Bunge Foundation BBS, University of Antwerp UIA, Antwerpen, Belgium
Hum Mol Genet 8:1529-40. 1999..Our data indicate that in the case of intron 4 mutation, the AD pathophysiology results from the presence of the PSEN1 T113-114ins protein comparable with cases carrying dominant PSEN1 missense mutations...
- Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer diseaseM Cruts
Laboratory of Neurogenetics, Flanders Interuniversity Institute for Biotechnology VIB, Born Bunge Foundation BBS, University of Antwerp UIA, Department of Biochemistry, Antwerpen, Belgium
Hum Mol Genet 7:43-51. 1998..Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies...
- The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's diseaseK M Mattila
Karolinska Institute, Alzheimer s Disease Research Centre, KFC, Novum, Huddinge, Sweden
Ann Neurol 44:965-7. 1998..We also found the Glu318Gly mutation in 4 healthy aged controls (range, 74-87 years). We thus conclude that the mutation is most likely a rare polymorphism not related to AD...
- A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with early onset Alzheimer diseaseM G Ramírez-Dueñas
Departamento de Fisiologia, Universidad de Guadalajara, Jalisco, Mexico
Ann Genet 41:149-53. 1998..The pedigree analysis and the literature data strongly suggest an etiopathogenic relationship of the mutation with the disorder...
- Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease familiesK Kamino
Department of Geriatric Medicine, Osaka University Medical School, Japan
Neurosci Lett 208:195-8. 1996..Our results suggested the existence of a variety of PS-1 mutations, and that early-onset FAD with PS-1 mutations is highly penetrant and is only rarely subject to modulation by genetic or environmental modifying factors...
- Frontotemporal dementia with novel tau pathology and a Glu342Val tau mutationC F Lippa
Department of Neurology, Medical College of Pennsylvania Hahnemann University, Philadelphia 19129, USA
Ann Neurol 48:850-8. 2000....
- A new SPG4 mutation in a variant form of spastic paraplegia with congenital arachnoid cystsA Orlacchio
Laboratory of Neurogenetics, University of Rome Tor Vergata, Rome, Italy
Neurology 62:1875-8. 2004..A molecular study has revealed a novel missense mutation, T614I, in exon 17 of SPG4, which may play a role in both focal cortical dysgenesis and neurodegeneration of the motor neurons in the corticospinal tract...
- Association between presenilin-1 Glu318Gly mutation and familial Alzheimer's disease in the Australian populationK Taddei
Sir James McCusker Alzheimer s Disease Research Unit and University of Western Australia, Department of Surgery, Hollywood Private Hospital, Nedlands, Perth 6009, Australia
Mol Psychiatry 7:776-81. 2002..0%) or the Spanish population (5.3%). These findings show that the frequency of the Glu318Gly mutation is increased in FAD patients, suggesting a potential role as a genetic risk factor contributing to the pathogenesis of familial AD...
- Variable clinical symptoms in familial amyotrophic lateral sclerosis with a novel point mutation in the Cu/Zn superoxide dismutase geneM Ikeda
Department of Neurology, Gunma University School of Medicine, Maebashi, Japan
Neurology 45:2038-42. 1995..These results suggest that FALS from this novel I104F mutation shows considerable clinical variation...