Publications related to Site-Specific Hyperphosphorylation Inhibits, Rather than Promotes, Tau Fibrillization, Seeding Capacity, and Its Microtubule Binding

To target Tau pathologies, we must embrace and reconstruct their complexities

The accumulation of hyperphosphorylated fibrillar Tau aggregates in the brain is one of the defining hallmarks of Tauopathy diseases, including Alzheimer's disease. However, the primary events or molecules responsible for initiation of the pathological Tau ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2021

Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau

Hilal Lashuel, Anass Chiki, Nadine Aït Bouziad, Galina Limorenko

The microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Increasing evidence suggests that post-translational modifications play critical roles in regulating Tau's norma ...

2020

Anti-Aβ antibodies bound to neuritic plaques enhance microglia activity and mitigate tau pathology

Philippe Colin, Bernard Schneider, Vanessa Laversenne

The brain pathology of Alzheimer’s disease (AD) is characterized by the misfolding and aggregation of both the amyloid beta (Aβ) peptide and hyperphosphorylated forms of the tau protein. Initial Aβ deposition is considered to trigger a sequence of deleteri ...

2020

Single Posttranslational Modifications in the Central Repeat Domains of Tau4 Impact its Aggregation and Tubulin Binding

Hilal Lashuel, Mahmood Haj Yahya

A variety of methods have been employed to study the impact of posttranslational modifications on Tau protein function. Here, a semisynthesis strategy is described that enables selective modification within the central repeat domain of Tau4 (residues 291-3 ...

Wiley-VCH Verlag GmbH2019

Application of anti-amyloid beta immunization using encapsulated cell technology in mouse models of Alzheimer's disease

Vanessa Laversenne

Alzheimer's disease (AD) is the most common form of dementia in the elderly. AD is characterized by the deposition of two aggregated proteins: Amyloid beta (Aß) and hyperphosphorylated tau. Accumulations of these proteins are thought to be the signature ...

EPFL2019

A method for preparing phfs-like tau aggregates

Hilal Lashuel, Nadine Aït Bouziad

The invention relates to a method for preparing PHFs-like Tau aggregates and to a method for identifying compounds that are inhibitors of Tau protein aggregation, blockers of Tau seeding and propagation, and imaging agents that specifically bind PHF. ...

2019

A viral vector based in vivo model of tauopathy to explore therapeutic strategies against tau pathology

Sameer Mohammad Khaleel Nazeeruddin

Tauopathies are neurodegenerative diseases whose common pathological feature is the intraneuronal accumulation of tau aggregates. Tau protein has various roles in the neuron, among which stabilization of microtubules (MT), regulation of synaptic activity o ...

EPFL2019

alpha-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson's disease

Hilal Lashuel, Anne-Laure Mahul Mellier

A compelling link is emerging between the posttranslational modification O-GlcNAc and protein aggregation. A prime example is alpha-synuclein, which forms toxic aggregates that are associated with neurodegeneration in Parkinson's and related diseases. alph ...

National Academy of Sciences2019

Protein Semisynthesis Provides Access to Tau Disease-Associated Post-translational Modifications (PTMs) and Paves the Way to Deciphering the Tau PTM Code in Health and Diseased States

Hilal Lashuel, Mahmood Haj Yahya

The microtubule-associated protein Tau plays a central role in neurodegeneration and is a leading therapeutic target for the treatment of Alzheimer’s disease (AD). Several lines of evidence suggest that post-translational modifications (PTMs) regulate the ...

2018

Calpain-mediated tau fragmentation is altered in Alzheimer's disease progression

Andrea Pfeifer, Andreas Muhs

The aggregation of intracellular tau protein is a major hallmark of Alzheimer's disease (AD). The extent and the stereotypical spread of tau pathology in the AD brain are correlated with cognitive decline during disease progression. Here we present an in-d ...

Nature Research2018

Stabilization of overlapping biofilaments by passive crosslinkers

Ignacio Pagonabarraga Mora

The formation, maintenance and reorganization of the cytoskeletal filament network is essential for a number of cellular processes. While the crucial role played by active forces generated by motor proteins has been studied extensively, only recently the i ...

IOP Publishing - EPL Association2018

Sequence and structural determinants of Tau aggregation and seeding capacity: Implications for Neurofibrillary Tangle formation and Tau toxicity in Alzheimer's disease

Nadine Aït Bouziad

Despite decades of research in Alzheimerâ s disease (AD), no treatment has been found to efficiently prevent or cure its progression. The microtubule binding protein Tau plays central roles in the pathogenesis of AD and is found, in the form of paired hel ...

EPFL2017

Discovery and characterization of novel stable tau oligomeric complexes: Implications for the role of Tau/phospholipid interactions in regulating its functions in health and disease

Hilal Lashuel, Nadine Aït Bouziad, Gizem Zorludemir, Anne-Laure Mahul Mellier

The microtubule-associated protein Tau plays a central role in the pathogenesis of Alzheimer's disease. Although Tau interaction with membranes is thought to affect some of its physiological functions and its aggregation properties, the sequence determinan ...

Nature Publishing Group2017

Microtubule-Binding R3 Fragment from Tau Self-Assembles into Giant Multistranded Amyloid Ribbons

Raffaele Mezzenga, Hilal Lashuel, Nadine Aït Bouziad

Tau protein and its fragments self-assemble into amyloid fibrils in the presence of polyanions, such as heparin. By combining microscopy, scattering, and spectroscopy techniques, we studied the aggregation of the 26-mer Tau-derived peptide alone, Tau306-32 ...

Wiley-VCH Verlag GmbH2016

The Human Centriolar Protein CEP135 Contains a Two-Stranded Coiled-Coil Domain Critical for Microtubule Binding

Pierre Gönczy, Paul Guichard, Georgios Hatzopoulos

Centrioles are microtubule-based structures that play important roles notably in cell division and cilium biogenesis. CEP135/Bld10p family members are evolutionarily conserved microtubule-binding proteins important for centriole formation. Here, we analyze ...

Elsevier2016

Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth

Pierre Gönczy, Mary-Claude Croisier-Coeytaux, Nicola Jane Dynes, Ashwani Sharma

Centrioles are fundamental and evolutionarily conserved microtubule-based organelles whose assembly is characterized by microtubule growth rates that are orders of magnitude slower than those of cytoplasmic microtubules. Several centriolar proteins can int ...

Cell Press - Elsevier2016

Mechanisms of centrosome separation in C. elegans

Alessandro De Simone

Centrosomes are the major microtubule organizing centers of animal cells. The two centrosomes present at the onset of mitosis must separate in a timely fashion along the nuclear envelope to ensure proper bipolar spindle assembly and thus genome stability. ...

EPFL2016

Aurora A kinase regulates proper spindle positioning in C-elegans and in human cells

Pierre Gönczy, Coralie Busso, Sachin Kotak

Accurate spindle positioning is essential for error-free cell division. The one-cell Caenorhabditis elegans embryo has proven instrumental for dissecting mechanisms governing spindle positioning. Despite important progress, how the cortical forces that act ...

2016

NuMA interacts with phosphoinositides and links the mitotic spindle with the plasma membrane

Pierre Gönczy, Coralie Busso, Sachin Kotak

The positioning and the elongation of the mitotic spindle must be carefully regulated. In human cells, the evolutionary conserved proteins LGN/Gai1-3 anchor the coiled-coil protein NuMA and dynein to the cell cortex during metaphase, thus ensuring proper s ...

2014

Clathrin regulates centrosome positioning by promoting acto-myosin cortical tension in C. elegans embryos

Pierre Gönczy, Kalyani Thyagarajan, Sylvain Träger, Alessandro De Simone

Regulation of centrosome and spindle positioning is crucial for spatial cell division control. The one-cell Caenorhabditis elegans embryo has proven attractive for dissecting the mechanisms underlying centrosome and spindle positioning in a metazoan organi ...

Company Of Biologists Ltd2014