Publications de Hilal Lashuel | EPFL Graph Search

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More than a century has passed since pathological protein aggregates were first identified in the brains of patients with neurodegenerative diseases (NDDs). Yet, we still do not have effective therapies to treat or slow the progression of these devastating ...

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is considered an attractive therapeutic target in multiple inflammatory and autoimmune disorders. In addition to its known biologic activities, MIF can also function as a tautomerase ...

Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with age-associated neurodegenerative disorders such as Alzheimer and Parkinson disease ( ...

α-Synuclein can be degraded by both the ubiquitin-proteasomal system and the chaperone-lysosomal system. However, the switching mechanism between the two pathways is not clearly understood. In our study, we investigated the mutual association between the b ...

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 ...

Phosphorylation of the N‐terminal domain of the huntingtin (HTT ) protein has emerged as an important regulator of its localization, structure, aggregation, clearance and toxicity. However, validation of the effect of bona fide phosphorylation in vivo and ...

Amyloid diseases are global epidemics with profound health, social and economic implications and yet remain without a cure. This dire situation calls for research into the origin and pathological manifestations of amyloidosis to stimulate continued develop ...

Despite the strong evidence linking the aggregation of the Huntingtin protein (Htt) to the pathogenesis of Huntington’s disease (HD), the mechanisms underlying Htt aggregation and neurodegeneration remain poorly understood. Herein, we investigated the ultr ...

Continuous fluidic sampling systems allow collection of brain biomarkers in vivo. Here, we propose a new sequential and intermittent sampling paradigm using droplets, called Droplet on Demand (DoD). It is implemented in a microfabricated neural probe and a ...

Super-resolution fluorescence microscopy provides unprecedented insight into cellular and subcellular structures. However, going beyond the diffraction barrier comes at a price since most far-field super-resolution imaging techniques trade temporal for spa ...

Background: The development of therapeutics for Parkinson's disease (PD) requires the establishment of biomarker assays to enable stratifying patients, monitoring disease progression, and assessing target engagement. Attempts to develop diagnostic assays b ...

The invention relates to use of an aerolysin nanopore for the discrimination of different protein isoforms bearing different post-translational modifications (PTMs) and to methods for detecting adverse medical conditions associated with the presence of pep ...

α-Synuclein aggregates in Lewy bodies and plays a central role in the pathogenesis of a group of neurodegenerative disorders, known as "Synucleinopathies", including Parkinson's disease. Parkin mutations result in loss of parkin E3-ubiquitin ligase activit ...

Protein fibrillization is implicated in the pathogenesis of most, if not all, age-associated neurodegenerative diseases, but the mechanism(s) by which it triggers neuronal death is unknown. Reductionist in vitro studies suggest that the amyloid protofibril ...

Several lines of research point to a key role of low oxygen supply (hypoxia) in Parkinson's disease pathogenesis. Although severe hypoxia is detrimental for the brain, physiological adaptations to mild hypoxia are neuroprotective. Herein we discuss, how ne ...

Brain aging and neurodegeneration are associated with prominent microglial reactivity and activation of innate immune response pathways, commonly referred to as neuroinflammation. One such pathway, the type I interferon response, recognizes viral or mitoch ...

Aggregation and fibril formation of the amyloid-β (Aβ) peptides play a pivotal role in the pathogenesis of Alzheimer's disease (AD). The missing links on the pathway to Aβ oligomerization, fibril formation, and neurotoxicity in AD remain the identity of th ...

Hilal Lashuel

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Rethinking protein aggregation and drug discovery in neurodegenerative diseases: Why we need to embrace complexity?

Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action

The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease

Phosphorylation of α-synuclein is crucial in compensating for proteasomal dysfunction

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

TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

Half a century of amyloids: past, present and future

The role of post-translational modification (phosphorylation) in modulating alpha-synuclein, structure, aggregation and toxicity

Nuclear and cytoplasmic huntingtin inclusions exhibit distinct biochemical composition, interactome and ultrastructural properties

On-Demand Nanoliter Sampling Probe for the Collection of Brain Fluid

Combined Multi-Plane Tomographic Phase Retrieval and Stochastic Optical Fluctuation Imaging for 4D Cell Microscopy

Comparative Analysis of Total Alpha-Synuclein (alpha SYN) Immunoassays Reveals That They Do Not Capture the Diversity of Modified alpha SYN Proteoforms

Investigation of alpha-synuclein post-translational modifications in idiopathic Parkinson's disease and multiple system atrophy

The role of PTM crosstalks in Httex1 structure, aggregation and membrane interaction

Uses of aerolysin nanopores

Parkinson-related parkin reduces α-Synuclein phosphorylation in a gene transfer model

Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins?

Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease?

Activation of the STING-dependent type I interferon response reduces microglial reactivity and neuroinflammation

Establishing the links between Aβ aggregation and cytotoxicity in vitro using biophysical approaches