Protein Semisynthesis Provides Access to Tau Disease-Associated Post-translational Modifications (PTMs) and Paves the Way to Deciphering the Tau PTM Code in Health and Diseased States

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

Hilal Lashuel, Matteo Dal Peraro, Luciano Andres Abriata, Lucien Fabrice Krapp, Anass Chiki, Driss Boudeffa, Iman Rostami, Rajasekhar Kolla, Zhidian Zhang

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 ...

2021

An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease

Mojgan Masoodi, Christopher Clark

Background Multiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypot ...

2021

The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation

Helen Lindsay

Liquid-liquid phase separation (LLPS) of proteins and RNAs has emerged as the driving force underlying the formation of membrane-less organelles. Such biomolecular condensates have various biological functions and have been linked to disease. The protein F ...

2021

Reverse engineering Lewy bodies: how far have we come and how far can we go?

Hilal Lashuel, Mohamed Bilal Fares, Somanath Jagannath

Lewy bodies (LBs) are α-synuclein (α-syn)-rich intracellular inclusions that are an important pathological hallmark of Parkinson disease and several other neurodegenerative diseases. Increasing evidence suggests that the aggregation of α-syn has a central ...

2021

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

Hilal Lashuel

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 ...

2021

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration

Hilal Lashuel, Sonia Donzelli

Alteration to endoplasmic reticulum (ER) proteostasis is observed in a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteost ...

2021

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, Jonathan Jean-Pierre Ricci, Andreas Reif, Rajasekhar Kolla, Iman Rostami, 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

TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin

Pierre Gönczy, Coralie Busso, Benita Wolf, Fernando Romero Balestra, Tessa Vivianne Averink, Alizée Buff

TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. TRIM37 depletion from tissue culture cells results in supernumerary foci bearing the centriolar protein Centrin. Here, we chara ...

2021

FTLD-TDP assemblies seed neoaggregates with subtype-specific features via a prion-like cascade

Henning Paul-Julius Stahlberg, Amanda Jennifer Lewis, Marta Di Fabrizio, Julien Weber

Morphologically distinct TDP-43 aggregates occur in clinically different FTLD-TDP subtypes, yet the mechanism of their emergence and contribution to clinical heterogeneity are poorly understood. Several lines of evidence suggest that pathological TDP-43 fo ...

WILEY2021

Interventions for Softening Can Lead to Hardening of Opinions: Evidence from a Randomized Controlled Trial

Robert West, Andreas Oliver Spitz, Ahmad Abu-Akel

Motivated by the goal of designing interventions for softening polarized opinions on the Web, and building on results from psychology, we hypothesized that people would be moved more easily towards opposing opinions when the latter were voiced by a celebri ...

ASSOC COMPUTING MACHINERY2021

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