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Hilal Lashuel

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Related publications (155)

The novel Parkinson's disease linked mutation G51D attenuates in vitro aggregation and membrane binding of alpha-synuclein, and enhances its secretion and nuclear localization in cells

Hilal Lashuel, Ana Jovicic, Martial Mbefo Kamdem, Nadine Aït Bouziad, Mohamed Bilal Fares

A novel mutation in the alpha-Synuclein (alpha-Syn) gene "G51D" was recently identified in two familial cases exhibiting features of Parkinson's disease (PD) and multiple system atrophy (MSA). In this study, we explored the impact of this novel mutation on ...

Oxford University Press2014

Alpha-synuclein Post-translational Modifications as Potential Biomarkers for Parkinson Disease and Other Synucleinopathies

Bruno Claude Daniel Fauvet, Hilal Lashuel, Adrian Schmid, Marc Moniatte

The development of novel therapies against neurodegenerative disorders requires the ability to detect their early, presymptomatic manifestations in order to enable treatment before irreversible cellular damage occurs. Precocious signs indicative of neurode ...

Amer Soc Biochemistry Molecular Biology Inc2013

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

Hilal Lashuel

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 ...

Academic Press Inc Elsevier Science2012

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

Hilal Lashuel, Mohammad Asad Jan Qureshi

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 ...

2012

Characterization of semisynthetic and naturally Nα-acetylated α-synuclein in vitro and in intact cells: implications for aggregation and cellular properties of α-synuclein

Bruno Claude Daniel Fauvet, Hilal Lashuel, Mohamed Bilal Fares

N-terminal acetylation is a very common post-translational modification, although its role in regulating protein physical properties and function remains poorly understood. α-Synuclein (α-syn), a protein that has been linked to the pathogenesis of Parkinso ...

Amer Soc Biochemistry Molecular Biology Inc2012

Discovery and Structure Activity Relationship of Small Molecule Inhibitors of Toxic β-Amyloid-42 Fibril Formation

Andrea Pfeifer, Hilal Lashuel, Mohammad Asad Jan Qureshi, Andreas Muhs, Annalisa Ansaloni, Paolo Paganetti, Magdalena Zweckstetter

Increasing evidence implicates Aβ peptides self-assembly and fibril formation as crucial events in the pathogenesis of Alzheimer disease. Thus, inhibiting Aβ aggregation, among others, has emerged as a potential therapeutic intervention for this disorder. ...

Amer Soc Biochemistry Molecular Biology Inc2012

Characterization of Molecular Determinants of the Conformational Stability of Macrophage Migration Inhibitory Factor: Leucine 46 Hydrophobic Pocket

Ursula Röthlisberger, Bruno Claude Daniel Fauvet, Hilal Lashuel, Hajer Ouertatani-Sakouhi, Michele Cascella, Farah El Turk, Marilisa Neri, Florence Pojer, Amer Ashrafi, Min Kyu Cho, Magdalena Zweckstetter

Macrophage Migration Inhibitory Factor (MIF) is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer f ...

Public Library of Science2012

Reactive oxidative species enhance amyloid toxicity in APP/PS1 mouse neurons

Hilal Lashuel, Yao Zhang

To investigate whether intracellular amyloid beta (iA beta) induces toxicity in wild type (WT) and APP/PS1 mice, a mouse model of Alzheimer's disease. ...

2012

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

Loay Awad, Bruno Claude Daniel Fauvet, Hilal Lashuel, Mirva Hejjaoui

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 ...

Elsevier2012

Elucidating the role of C-terminal post-translational modifications using protein semisynthesis strategies: α-synuclein phosphorylation at tyrosine 125

Michel Prudent, Bruno Claude Daniel Fauvet, Hilal Lashuel, Mirva Hejjaoui, Filip Vercruysse, Yao Zhang

Despite increasing evidence that supports the role of different post-translational modifications (PTMs) in modulating α-synuclein (α-syn) aggregation and toxicity, relatively little is known about the functional consequences of each modification and whethe ...

2012

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

Maria del Carmen Sandi Perez, Hilal Lashuel, Lisa Conboy, Jorge Eduardo Castro Cifuentes

Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokin ...

Nature Publishing Group2011

Phosphorylation of alpha-Synuclein at Y125 and S129 Alters Its Metal Binding Properties: Implications for Understanding the Role of alpha-Synuclein in the Pathogenesis of Parkinson's Disease and Related Disorders

Hubert Girault, Michel Prudent, Bruno Claude Daniel Fauvet, Hilal Lashuel, Yu Lu

alpha-Synuclein (alpha-syn) is a 140-amino acid protein that plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. However, the molecular determinants that are responsible for triggering and/or propagating alpha- ...

American Chemical Society2011

Method and compositions for inhibition of macrophage migration inhibitory factor (mif)

Hilal Lashuel, Hajer Ouertatani-Sakouhi

The present invention relates to methods for inhibition of tautomerase activity of macrophage migration inhibitory factor (MIF). The invention further relates to substances for irreversibly covalently binding to MIF for inhibition of tautomerase activity. ...

2011

Arab world needs its science diaspora

Hilal Lashuel

2011

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

Bruno Claude Daniel Fauvet, Hilal Lashuel, Hajer Ouertatani-Sakouhi, Farah El Turk, Min Kyu Cho, Magdalena Zweckstetter

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 ...

American Society for Biochemistry and Molecular Biology2010

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

Hilal Lashuel, Saviana Di Giovanni

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 ...

Elsevier2010

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

Hilal Lashuel, Mohammad Asad Jan Qureshi

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 ...

Nature Publishing Group2010

Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions

Patrick Aebischer, Bernard Schneider, Hilal Lashuel, Adrian Schmid, Marc Moniatte, Diego Chiappe, Abid Oueslati, Magdalena Zweckstetter

Increasing evidence suggests that phosphorylation may play an important role in the oligomerization, fibrillogenesis, Lewy body (LB) formation, and neurotoxicity of alpha-synuclein (alpha-syn) in Parkinson disease. Herein we demonstrate that alpha-syn is p ...

2010

An integrative in silico methodology for the identification of modulators of macrophage migration inhibitory factor (MIF) tautomerase activity

Bruno Claude Daniel Fauvet, Hilal Lashuel, Hajer Ouertatani-Sakouhi, Farah El Turk

Macrophage migration inhibitory factor (MIF) is a major proinflammatory cytokine that has been increasingly implicated in the pathogenesis of several inflammatory, autoimmune, infectious and oncogenic diseases. Accumulating evidence suggests that the tauto ...

Elsevier2010

Phosphorylation of synucleins by members of the Polo-like kinase family

Harald Hirling, Hilal Lashuel, Martial Mbefo Kamdem, Abid Oueslati, Magdalena Zweckstetter

Phosphorylation of alpha-synuclein (alpha-syn) at Ser-129 is a hallmark of Parkinson disease and related synucleinopathies. However, the identity of the natural kinases and phosphatases responsible for regulating alpha-syn phosphorylation remain unknown. H ...

American Society for Biochemistry and Molecular Biology2010

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