Ronald Melki

This study identifies PODXL as a suppressor of α-synuclein fibril uptake in neurons, highlighting its glycan-dependent surface properties and interaction with MME.

This study shows that disrupting sphingolipid metabolism reduces endolysosomal membrane fluidity, leading to rupture and tau aggregation, which can be mitigated by unsaturated fatty acids.

This study develops Syn-specific CAR iTregs that reduce neuroinflammation and proteinopathy in PD mice by selectively targeting aggregated α-Synuclein.

Proximity proteomics in PFF-seeded mouse olfactory bulb shows aggregated phospho-S129 alpha-synuclein mostly reprioritizes existing interactions toward axon-glia, myelin and proteostasis proteins, with a conserved 107-protein signature.

The paper analyzes 400 cryo-EM structures of amyloid fibrils to identify shared and unique surface pockets, showing pocket-level convergence across polymorphs and proteins, and proposes a framework for selective ligand targeting.

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.

The paper identifies BCL-XL as a potential regulator of the neurovascular unit in Parkinson's disease through systematic screening of -Synuclein strain responses in pericytes.

This study identifies structural and functional differences in alpha-synuclein fibrils from Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy, linking these differences to disease-specific cellular responses and potential therapeutic targets.

The paper shows that different structures of alpha-synuclein fibrils affect how Hsc70 chaperones disaggregate them, influencing protein quality control and aggregation.

This study evaluates PHP.eB AAVs for reducing alpha-synuclein burden in a mouse model of alpha-synucleinopathies, showing reduced pathology and motor deficits.

The paper uses CRISPR screens to identify OXR1 and EMC4 as modifiers of α-synuclein aggregation in Parkinson's disease and related synucleinopathies.

This study shows that alpha-synuclein aggregates are resistant to phosphatase dephosphorylation and introduces a method using calf intestinal phosphatase (CIAP) to specifically detect aggregated PSER129 in biological samples.

The study tests whether GBA1 mutations or mouse genotype affect alpha-synuclein seeding in mice, finding no significant influence on seeding efficacy or pathology spread.

This paper introduces a structural proteomic pipeline to study anti-amyloidogenic compounds' mechanisms in vitro and in situ, revealing off-target effects and structural interactions with α-Synuclein.

The paper investigates how Parkinson's disease-derived α-synuclein fibrils combined with inflammatory factors drive a neurotoxic microglial phenotype.

The paper uses FLIM to study α-Syn polymorphs in cells, showing distinct fluorescence lifetimes and differential processing by clearance pathways, leading to increased seeding capacity.

This study shows that AAV-mediated delivery of a novel anti-aggregated alpha-synuclein antibody improves survival in a mouse model of alpha-synucleinopathies.

This study investigates how microglia and astrocytes internalize and sort brain-derived exosomes, showing differential uptake efficiency and endosomal trafficking of exosome-associated alpha-synuclein.

This study shows human pericytes degrade different strains of alpha-synuclein aggregates in vitro, with varying efficiency depending on the strain and origin of the pericytes.

This study examines how α-synuclein and β-amyloid assemblies affect endosomal and lysosomal transport in mouse cortical neurons, revealing differential impacts on transport parameters and trajectory lengths.

This study shows that activating the JAK2-STAT3 pathway in astrocytes reduces mutant Huntingtin aggregates and improves disease outcomes in Huntington's disease models.

This study shows poly-GA DPRs are taken up by astrocytes via endocytosis, spread to motor neurons, and cause axonal swellings through lysosomal dysfunction.

This study uses a novel microfluidic system to investigate how alpha-synuclein aggregates spread between neurons, finding that synaptic connectivity does not significantly affect transfer efficiency.

Three fibril polymorphs, amplified from Parkinson's and multiple system atrophy brain homogenate by PMCA, adopt folds unlike any published alpha-synuclein arrangement; their disease relevance is untested.

This study shows LAG3 is not expressed in human and mouse neurons and does not worsen α-synuclein pathology in vitro or in vivo.

This study shows that different a-Synuclein strains influence MSA progression through central and peripheral immune mechanisms, with strain-dependent effects on neurodegeneration and glial responses.

This study shows that the Hsp70 disaggregation machinery disassembles Tau fibrils, generating small seeding-competent Tau species that can drive aggregation.

The paper reports two new polymorphic structures of alpha-synuclein fibrils solved by cryo-EM, showing distinct structural features and interactions compared to previous structures.

This study shows that LRRK2 modifies α-syn aggregation and spread in both mouse and human models, suggesting potential therapeutic targets for Parkinson's disease.