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

Related publications (26)

A New Chemoenzymatic Semisynthetic Approach Provides Insight into the Role of Phosphorylation beyond Exon1 of Huntingtin and Reveals N-Terminal Fragment Length-Dependent Distinct Mechanisms of Aggregation

Hilal Lashuel, Rajasekhar Kolla, Jonathan Jean-Pierre Ricci, Andreas Reif, Gopinath Pushparathinam

Huntington’s disease is a neurodegenerative dis- order caused by the expansion of a polyglutamine repeat (>36Q) in the N-terminal domain of the huntingtin protein (Htt), which renders the protein or fragments thereof more prone to aggregate and form inclus ...

2021

Applying Peptide and Protein Synthesis to Study Post-translational Modifications in Epigenetics and Beyond

Beat Fierz

Epigenetics research focuses on the study of heritable gene regulatory mechanisms that do not involve changes of the DNA sequence. Such mechanisms include post-translational modifications of histone proteins that organize the genome in the nucleus into a n ...

2021

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

Hilal Lashuel, Galina Limorenko

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

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

Hilal Lashuel, Raffaele Mezzenga, 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

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

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

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

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

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

Bernard Schneider, Philippe André Guy Colin, 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 ...

BioMed Central2020

Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth

Ashwani Sharma, Pierre Gönczy, Mary-Claude Croisier-Coeytaux

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

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

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

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

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

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

Focal expression of adeno-associated viral-mutant tau induces widespread impairment in an APP mouse model

Patrick Aebischer, Bernard Schneider, Jean-Charles Bensadoun

Adeno-associated virus serotype 6 (AAV6) viral vectors encoding mutant and normal tau were used to produce focal tau pathology. Two mutant forms of tau were used; the P301S tau mutation is associated with neurofibrillary tangle formation in humans, and the ...

Elsevier Science Inc2013

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

Mechanisms of spindle positioning: cortical force generators in the limelight

Pierre Gönczy, Sachin Kotak

Correct positioning of the spindle governs placement of the cytokinesis furrow and thus plays a crucial role in the partitioning of fate determinants and the disposition of daughter cells in a tissue. Converging evidence indicates that spindle positioning ...

2013

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

Co-pathological states of tau proteins in a 3D micropatterned neural cell culture

Serena Brando, Philippe Renaud, Anja Kunze, Robert Meissner

In vitro studies of Alzheimer’s disease are based on homogenously seeded neural cells. These studies reveal molecular pathway mechanism related to neurite degeneration, but they cannot analyze interactions between diseased and healthy cells. Furthermore, t ...

2011