Publications de Magdalena Zweckstetter

Alpha-synuclein research: defining strategic moves in the battle against Parkinson's disease

With the advent of the genetic era in Parkinson's disease (PD) research in 1997, alpha-synuclein was identified as an important player in a complex neurodegenerative disease that affects >10 million people worldwide. PD has been estimated to have an econom ...

NATURE RESEARCH2021

Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies

Hilal Lashuel, Magdalena Zweckstetter, Michael Heinrich

α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of th ...

Oxford University Press2017

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

Hilal Lashuel, Bruno Claude Daniel Fauvet, Magdalena Zweckstetter, Sebastian Kugler

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 ( ...

2017

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

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

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

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

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

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

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

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

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

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

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

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

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

A new class of isothiocyanate-based irreversible inhibitors of macrophage migration inhibitory factor

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

Macrophage migration inhibitory factor (MIF) is a homotrimeric multifunctional proinflammatory cytokine that has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. Current therapeutic strategies for targeting MIF focus on ...

American Chemical Society2009

Structural properties of pore-forming oligomers of alpha-synuclein

Hilal Lashuel, Magdalena Zweckstetter, Min Kyu Cho, Ajay Kumar

Soluble oligomers are potent toxins in many neurodegenerative diseases, but little is known about the structure of soluble oligomers and their structure-toxicity relationship. Here we prepared on-pathway oligomers of the 140-residue protein alpha-synuclein ...

American Chemical Society2009