SFU

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Alectos Supports NSERC Funding for Prof. A.J. Bennet at SFU

Feb 11, 2016 – Alectos today announced its support for NSERC funding for the group of Prof. A.J. Bennet at Simon Fraser University, Department of Chemistry, in a project titled “Fundamental Studies on the Biochemical Mechanism of Chemical Chaperoning of Glucocerebrosidase”. Parkinson's disease is a worldwide health problem that has been linked to deficiencies in [...]

February 11th, 2016|Tags: , , , , |

Alectos Engages As Industry Partner in the Canadian Glycomics Network (GlycoNet)

Feb 17, 2015 – Alectos today announced its support as an industry partner in the new Canadian Glycomics Network (GlycoNet), unveiled this month by Minister of Health Rona Ambrose with a commitment of $27.3 million in federal funding over five years. GlycoNet’s vision is to link academic, government and industry partners to deliver solutions to [...]

February 17th, 2015|Tags: , , |

Structures of lactate dehydrogenase A (LDHA) in apo, ternary and inhibitor-bound forms

Lactate dehydrogenase (LDH) is an essential metabolic enzyme that catalyzes the interconversion of pyruvate and lactate using NADH/NAD(+) as a co-substrate. Many cancer cells exhibit a glycolytic phenotype known as the Warburg effect, in which elevated LDH levels enhance the conversion of glucose to lactate, making LDH an attractive therapeutic target for oncology. Two known [...]

January 23rd, 2015|Tags: , , , |

Fluorescence-quenched substrates for live cell imaging of human glucocerebrosidase activity

Deficiency of the lysosomal glycoside hydrolase glucocerebrosidase (GCase) leads to abnormal accumulation of glucosyl ceramide in lysosomes and the development of the lysosomal storage disease known as Gaucher's disease. More recently, mutations in the GBA1 gene that encodes GCase have been uncovered as a major genetic risk factor for Parkinson's disease (PD). Current therapeutic strategies [...]

January 15th, 2015|Tags: , , |

Alectos Announces Preclinical Results in TAPP Mouse Model of Alzheimer’s Disease

Oct 26, 2014 – Alectos today announced publication of preclinical studies showing that pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in the TAPP mouse model of Alzheimer’s disease. For details, see: Yuzwa, S.A. et al. Mol Neurodegener 9:42 (2014).

October 26th, 2014|Tags: , , , , , , , |

Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice

BACKGROUND: Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. It remains unknown, however, if O-GlcNAc can influence the formation of [...]

October 26th, 2014|Tags: , , , , , , , |

The emerging link between O-GlcNAc and Alzheimer disease

Regional glucose hypometabolism is a defining feature of Alzheimer disease (AD). One emerging link between glucose hypometabolism and progression of AD is the nutrient-responsive post-translational O-GlcNAcylation of nucleocytoplasmic proteins. O-GlcNAc is abundant in neurons and occurs on both tau and amyloid precursor protein. Increased brain O-GlcNAcylation protects against tau and amyloid-β peptide toxicity. Decreased O-GlcNAcylation [...]

October 21st, 2014|Tags: , , , , , , , , , , |

Alectos Announces Preclinical Data for Novel Cancer Metabolism Target

May 22, 2014 – Alectos today announced publication of preclinical studies showing that both knockdown and pharmacological inhibition of O-GlcNAc transferase (OGT) result in reduced metabolic output, increased apoptosis, and impaired survival in tumor cells.  This data strongly supports OGT as a novel cancer metabolism target. For details, see: Ferrer, C.M. et al. Mol Cell [...]

May 22nd, 2014|Tags: , , , |

O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer’s disease and beyond

Alzheimer disease (AD) is a growing problem for aging populations worldwide. Despite significant efforts, no therapeutics are available that stop or slow progression of AD, which has driven interest in the basic causes of AD and the search for new therapeutic strategies. Longitudinal studies have clarified that defects in glucose metabolism occur in patients exhibiting [...]

April 24th, 2014|Tags: , , , , , , , , |

O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers

The aggregation of the microtubule-associated protein tau into paired helical filaments to form neurofibrillary tangles constitutes one of the pathological hallmarks of Alzheimer's disease. Tau is post-translationally modified by the addition of N-acetyl-D-glucosamine O-linked to several serine and threonine residues (O-GlcNAc). Previously, increased O-GlcNAcylation of tau has been shown to block the accumulation of tau [...]

January 18th, 2014|Tags: , , , |