Publications by Hilal Lashuel | EPFL Graph Search

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Reconstitution of TDP-43 filaments that exhibit sequence and morphological features similar to those found in the brain helps to uncover a new mechanism for the formation and propagation of pathology in amyotrophic lateral sclerosis and other neurodegenera ...

Parkinsons disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of intraneuronal inclusions consisting of aggregated and post-translationally modified a-synuclein (a-syn). Despite advances in the chemic ...

The amyloid cascade hypothesis, supported by strong evidence from genetics, pathology and studies using animal models, implicates amyloid-beta (Abeta) oligomerization and fibrillogenesis as central causative events in the pathogenesis of Alzheimer's diseas ...

The first exon of the Huntingtin protein (Httex1) is one of the most actively studied Htt fragments because its overexpression in R6/2 transgenic mice has been shown to recapitulate several key features of Huntington disease. However, the majority of bioph ...

Mutations in the TARDBP gene, which encodes the TDP-43 protein, account for only 3–5% of familial cases of amyotrophic lateral sclerosis and less than 1% of cases that are apparently idiopathic. However, the discovery of neuronal inclusions of TDP-43 as th ...

alpha-Synuclein aggregation and accumulation in Lewy bodies are implicated in progressive loss of dopaminergic neurons in Parkinson disease and related disorders. In neurons, the Hsp70s and their Hsp40-like J-domain co-chaperones are the only known compone ...

Sorting, transport, and autophagic degradation of proteins in endosomes and lysosomes, as well as the division of these organelles, depend on scission of membrane-bound tubulo-vesicular carriers. How scission occurs is poorly understood, but family protein ...

Die amyloide Selbstassemblierung von α‐Synuclein (αSyn) wird mit der Pathogenese der Parkinson‐Krankheit (PD) in Verbindung gebracht. Typ 2 Diabetes (T2D) hat sich kürzlich als Risikofaktor für PD herausgestellt. Kreuzinteraktionen zwischen den amyloidogen ...

The invention relates to methods for the preparation of method of preparation of Tau aggregates, including fibrils, fibrillar species, soluble and insoluble oligomeric species, new Tau aggregates and uses thereof. The invention further relates to the uses ...

Alpha-synuclein aggregation and mitochondrial dysfunction are main pathological hallmarks of Parkinson's disease (PD) and several other neurodegenerative diseases, collectively known as synucleinopathies. However, increasing evidence suggests that they may ...

Alpha-synuclein is a presynaptic protein of poorly understood function that is linked to both genetic and sporadic forms of Parkinson's disease. We have proposed that alpha-synuclein may function specifically at synaptic vesicles docked at the plasma membr ...

Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of the Huntingtin protein (Htt) have been shown to inhibit the aggregation and attenuate the toxicity of mutant Htt proteins in vitro and in various models of Huntington’s disea ...

Huntington’s disease is caused by expansion of a polyglutamine (polyQ) domain within exon 1 of the huntingtin gene (Httex1). A popular hypothesis is that the Httex1 protein undergoes sharp conformational changes as the polyQ length exceeds a threshold of 3 ...

A review. Studies on designed peptides that exhibit high tendencies for medium-induced conformational transitions have recently attracted much attention because structural changes are considered as mol. key processes in degenerative diseases. The exptl. ac ...

O-linked N-acetylglucosamine (O-GlcNAc) is an endogenous form of glycosylation that alters the structure of alpha-synuclein amyloid fibrils and attenuates their pathogenetic properties. The modified fibrils have a significantly reduced ability to seed the ...

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. ...

It has been more than a century since the first evidence linking the process of amyloid formation to the pathogenesis of Alzheimer's disease. During the last three decades in particular, increasing evidence from various sources (pathology, genetics, cell c ...

Parkinson's disease (PD) is a movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of intraneuronal inclusions called Lewy bodies, which are composed mainly of α-synuclein (α-syn). Selegiline (Sel) i ...

Accumulation and aggregation of misfolded alpha-synuclein is believed to be a cause of Parkinson's disease (PD). Phosphorylation of alpha-synuclein at S129 is known to be associated with the pathological misfolding process, but efforts to investigate the r ...

Background: There is increasing evidence that Parkinson's disease (PD) might start in the gut, thus involving and compromising also the enteric nervous system (ENS). At the clinical onset of the disease the majority of dopaminergic neurons in the midbrain ...

Hilal Lashuel

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Seeding the aggregation of TDP-43 requires post-fibrillization proteolytic cleavage

Elucidating the Role of Site-Specific Nitration of alpha-Synuclein in the Pathogenesis of Parkinson's Disease via Protein Semisynthesis and Mutagenesis

Preparation and characterization of toxic Abeta aggregates for structural and functional studies in Alzheimer's disease research

An Intein-based Strategy for the Production of Tag-free Huntingtin Exon 1 Proteins Enables New Insights into the Polyglutamine Dependence of Httex1 Aggregation and Fibril Formation

Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy

Stable -Synuclein Oligomers Strongly Inhibit Chaperone Activity of the Hsp70 System by Weak Interactions with J-domain Co-chaperones

Membrane scission driven by the PROPPIN Atg18

Multi‐Targeting Makrozyklische Peptide als Nanomolare Inhibitoren der Selbst‐ und Kreuznukleation der Amyloiden Selbstassemblierung von α‐Synuclein

Method of preparation of amyloidogenic protein aggregates and uses thereof

Fatal attraction-The role of hypoxia when alpha-synuclein gets intimate with mitochondria

Semisynthetic and in Vitro Phosphorylation of Alpha-Synuclein at Y39 Promotes Functional Partly Helical Membrane-Bound States Resembling Those Induced by PD Mutations

Investigating Crosstalk Among PTMs Provides Novel Insight Into the Structural Basis Underlying the Differential Effects of Nt17 PTMs on Mutant Httex1 Aggregation

Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths

Switch-peptides: from conformational studies to Alzheimer's disease

Post-translational glycosylation diminishes α-synuclein pathology formation

A method for preparing phfs-like tau aggregates

Chemical strategies for controlling protein folding and elucidating the molecular mechanisms of amyloid formation and toxicity

The anti-Parkinsonian drug selegiline delays the nucleation phase of α-synuclein aggregation leading to the formation of nontoxic species

Phospho-S129 Alpha-Synuclein Is Present in Human Plasma but Not in Cerebrospinal Fluid as Determined by an Ultrasensitive Immunoassay

Parkinson mice show functional and molecular changes in the gut long before motoric disease onset