Hilal Ahmed Lashuel

Ultrasensitive Detection of Alpha-Synuclein Oligomers in Human Plasma Using Optimized Nano-QuIC

This study develops an optimized Nano-QuIC platform to detect alpha-synuclein oligomers in human plasma with high sensitivity for early Parkinson's disease diagnosis.

De novo Design of Polymorph-Specific Binders Targeting α-Synuclein Fibrils

This study designs polymorph-specific binders for α-synuclein fibrils using a computational pipeline, demonstrating their utility as selective labeling agents without interfering with fibril dynamics.

A Microfluidic Platform for Whole-Membrane Integrity Profiling in Live Neuronal Cells

This study introduces a microfluidic platform to assess membrane integrity in live neuronal cells by measuring dielectric properties, showing its ability to detect different forms of alpha-synuclein's effects on membrane capacitance.

α-Synuclein Facilitates Spontaneous Dopamine Release in a Calcium- and Phosphorylation-Dependent Manner

This study shows α-synuclein modulates spontaneous dopamine release via calcium and phosphorylation-dependent mechanisms, independent of full-fusion recycling.

WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease

This study identifies WDR44 as a driver of de novo α-synuclein aggregation at the lysosomal membrane, linking early aggregation events to neuronal dysfunction in Parkinson's Disease.

A Site-Specific Organometallic Approach for Installing Tyrosine Phosphorylation Mimics to Decipher the Role of Phosphorylation in Alpha-Synuclein (aSyn) Aggregation and Seeding

This paper introduces a site-specific organometallic method to install tyrosine phosphorylation mimics in alpha-synuclein, revealing that di- and tri-phosphorylation slow aggregation and reduce seeding activity.

Recapitulating Parkinson's pathology in human iPSC dopaminergic neurons reveals new mechanistic insights into Lewy body formation and heterogeneity.

This study uses human iPSC-derived dopaminergic neurons to model Parkinson's Lewy body pathology without genetic modification, revealing mechanisms of aSyn aggregation and morphological diversity.

Defined human tri-lineage brain microtissues

The paper develops human tri-lineage brain microtissues composed of neurons, astrocytes, and microglia, showing they recapitulate cell-cell interactions and pathological processes.

Mapping the Structural Landscape of Amyloid Fibrils to Guide Polymorph-Specific Therapeutics

This paper introduces FibrilSite, a computational pipeline to identify structural features of amyloid fibrils, revealing conserved and polymorph-specific sites that guide drug discovery.

Huntingtin inclusion bodies have distinct immunophenotypes and ubiquitination profiles in the Huntington's disease human cerebral cortex

This study examines the immunophenotypic and ubiquitination diversity of Huntingtin inclusion bodies in Huntington's disease cerebral cortex, revealing heterogeneity in composition and degradation pathways.

Tissue Reconstruction with Generative AI

LUNA reconstructs tissue architecture from dissociated single-cell RNA-seq data using spatial priors learned from spatial transcriptomics, validating on mouse brain datasets and disease models.

Dissecting the differential role of C-terminal truncations in the regulation of aSyn pathology formation and the biogenesis of Lewy bodies

This study investigates how C-terminal truncations of alpha-synuclein (aSyn) affect Lewy body (LB) formation and pathology in Parkinson's disease by analyzing their role in fibril processing and aggregation.

Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases

This study reports the atomic structure of mouse α-synuclein fibrils and shows they differ structurally and functionally from human fibrils linked to Parkinson's and MSA.

Differential Effects of Posttranslational Modifications on the Membrane Interaction of Huntingtin Protein

This study investigates how posttranslational modifications affect the membrane interaction and helical structure of the N-terminal fragment of the huntingtin protein.

Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases

The paper develops and validates an expanded antibody panel to capture diverse alpha-synuclein conformations and modifications in Lewy body diseases.

Overexpression of human alpha-synuclein leads to dysregulated microbiome and metabolites with ageing in a rat model of Parkinson disease

This study shows that overexpression of human alpha-synuclein in rats leads to gut microbiome dysbiosis, altered metabolites, and aging-related changes that can be modulated by antibiotics.

Post-fibrillization nitration of alpha-synuclein abolishes its seeding activity and pathology formation in primary neurons and in vivo

This study shows that nitration of alpha-synuclein after fibrillization reduces its seeding activity and pathology formation in neurons and in vivo.

Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders

The paper investigates astrocytic alpha-synuclein pathology in Lewy body disorders, revealing unique post-translational modification signatures and distribution patterns.

On demand nanoliter sampling probe for collection of brain fluid

This paper introduces a new microfabricated neural probe that enables precise, transient-free sampling of brain extracellular fluid biomarkers in vivo and in vitro.

N-terminal mutant Huntingtin deposition correlates with CAG repeat length and disease onset, but not neuronal loss in Huntington's disease

This study screens antibodies against huntingtin (Htt) to analyze Htt distribution and aggregates in HD brain tissue, finding correlations between CAG repeat length and Htt aggregation, but not neuronal loss.

Comparative analysis of total alpha-synuclein (αSYN) immunoassays reveals that they do not capture the diversity of modified αSYN proteoforms

The paper compares three commercial alpha-synuclein immunoassays and finds they fail to capture the diversity of modified alpha-synuclein proteoforms.

Neighbouring modifications interfere with the detection of phosphorylated alpha-synuclein at Serine 129: Revisiting the specificity of pS129 antibodies

The paper shows that neighboring post-translational modifications affect the detection of phosphorylated alpha-synuclein at Serine 129 by existing antibodies.

Pathological relevance of post-translationally modified alpha-synuclein (pSer87, pSer129, nTyr39) in idiopathic Parkinson's disease and Multiple System Atrophy.

The paper examines post-translational modifications of alpha-synuclein in Parkinson's disease and Multiple System Atrophy using immunohistochemistry to identify predominant PTMs in pathological aggregates.

A novel mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein fibrils and recapitulates its pathological diversity

The paper investigates the effects of the E83Q mutation on alpha-synuclein aggregation and toxicity, finding it accelerates fibrillization and enhances pathological features in neuronal models.

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

The paper examines the biochemical composition, interactome, and ultrastructural properties of nuclear and cytoplasmic Htt inclusions in mammalian cells and neurons.

The structural basis of huntingtin (Htt) fibril polymorphism, revealed by cryo-EM of exon 1 Htt fibrils

This study uses cryo-EM to reveal the structural polymorphism of huntingtin exon1 fibrils, showing unique beta-hairpin arrangements and flanking domain organization.

The Nt17 domain and its helical conformation regulate the aggregation, cellular properties and neurotoxicity of mutant huntingtin exon 1

This study shows that the Nt17 domain regulates Httex1 aggregation, toxicity, and cellular uptake through its conformation and interaction with polyQ repeats.

A new chemoenzymatic semisynthetic approach provides novel insight into the role of phosphorylation beyond exon1 of Huntingtin and reveals N-terminal fragment length-dependent distinct mechanisms of aggregation

This paper investigates the aggregation mechanisms of different N-terminal Htt fragments and introduces a chemoenzymatic method for site-specific phosphorylation beyond Httex1.

Correlative light and electron microscopy reveals that mutant huntingtin dysregulates the endolysosomal pathway in presymptomatic Huntington's disease

This study uses correlative light and electron microscopy to show that mutant huntingtin accumulates in endolysosomal organelles in presymptomatic Huntington's disease, altering endolysosomal homeostasis.

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the unfolded protein response (UPR) in models of neurodegeneration

This study shows that forcing dimerization between ATF6f and XBP1s enhances UPR activity, reducing protein aggregation in neurodegenerative disease models.