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In a screen for cell cycle-regulated genes in the yeast Saccharomyces cerevisiae, we have identified a gene, EGT2, which is involved in cell separation in the G1 stage of the cell cycle. Transcription of EGT2 is tightly regulated in a cell cycle-dependent manner. Transcriptional levels peak at the boundary of mitosis and early G1 The transcription factors(More)
The neuronal protein tau, a member of the class of intrinsically disordered proteins, is characterized by the absence of any firm 3-D structure and high solubility when free in solution. The tau protein forms insoluble fibrils in the brain of people suffering from Alzheimer's disease (AD) and other tauopathies and plays a key role in the neurodegenerative(More)
We have previously demonstrated in a transgenic rat model of tauopathy that human misfolded truncated tau derived from Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo. We employed this model to investigate the impact of truncated tau expression levels on life span, neuronal loss and the final load of neurofibrillary tangles (NFTs)(More)
Tau protein is a member of microtubule-associated protein family. Under pathological conditions, tau undergoes multiple modifications that lead to the formation of insoluble deposits in neurons, resulting in neuronal dysfunction in several neurodegenerative disorders collectively called tauopathies, with Alzheimer's disease being the most frequent example.(More)
We have identified structural determinants on tau protein that are essential for pathological tau–tau interaction in Alzheimer’s disease (AD). These regulatory domains, revealed by monoclonal antibody DC8E8, represent a novel target for tau-directed therapy. In order to validate this target, we have developed an active vaccine, AADvac1. A tau peptide(More)
Neurofibrillary degeneration and neuronal loss represent key pathological hallmarks of Alzheimer's disease (AD). It has been demonstrated that the decrease of total neuronal numbers correlates with the presence of neurofibrillary degeneration in AD brain. In order to unravel the mechanism leading to the cell death in AD, we developed a stably transfected(More)
Numerous epidemiological studies demonstrate that genetic background modifies the onset and the progression of Alzheimer's disease and related neurodegenerative disorders. The efficacious influence of genetic background on the disease pathway of amyloid beta has been meticulously described in rodent models. Since the impact of genetic modifiers on the(More)
Alzheimer’s disease (AD) is the leading cause of dementia, a condition that gradually destroys brain cells and leads to progressive decline in mental functions. The disease is characterized by accumulation of misfolded neuronal proteins, amyloid and tau, into insoluble aggregates known as extracellular senile plaques and intracellular neurofibrillary(More)
Abnormal misfolded tau protein is a driving force of neurofibrillary degeneration in Alzheimer's disease. It has been shown that tau oligomers play a crucial role in the formation of intracellular neurofibrillary tangles. They are intermediates between soluble tau monomers and insoluble tau filaments and are suspected contributors to disease pathogenesis.(More)
Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer's disease (AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD, most(More)