Topic: synucleinopathies

The main pathological hallmark of Parkinson’s disease (PD) and related synucleinopathies is the presence of intracellular proteinaceous aggregates, enriched in the presynaptic protein alpha-Synuclein (α-Syn). α-Syn association with exosomes has been previously documented both as a physiological process of secretion and as a pathological process of disease transmission, however, critical information about the mechanisms governing this interplay is still lacking. To address this, we utilized the α-Syn preformed fibril (PFF) mouse model of PD, as a source of brain-derived exosome-enriched extrace

In synucleinopathies, α-synuclein (α-syn) is thought to exist within a dynamic equilibrium, comprising both α-syn oligomers (OSyn) and more aggregated forms. OSyn has been associated to neurodegeneration, neurotoxicity, and proinflammatory responses, even at low concentrations and is thought to be involved in Parkinson’s disease (PD) pathogenesis.To date, it is not clear whether the neurotoxicity exerted by α-syn aggregates is due to the presence of scattered oligomeric species, anticipating the formation of proper fibrillary α-syn, or whether it is sustained by α-syn species that are already

Transmission of misfolded α-synuclein between neurons is a key mechanistic feature of Parkinson’s and in the creation of Lewy pathology. Despite the prion-like nature of Parkinson’s, it is not yet known why some cell populations are resistant to pathology development. We hypothesise that an extracellular neuronal coat, the perineuronal net (PNN), could be a factor underlying neuronal resistance in Parkinson’s. A proteomic screen of extracellular brain lysate with PNN-derived glycans identified the entire synuclein family. Using surface plasmon resonance, the PNN glycans, heparin sulfate &

α-Synuclein (α-Syn) and Tau proteins are neuropathological hallmarks for synucleinopathies and tauopathies, respectively. Co-occurrence of a-Syn and tau aggregates was found in the post-mortem brains of the patients, suggesting a complex interplay between two proteins contributes to the diseases. Here, we explore the polymorphism of α-Syn and Tau cross-seeding with a correlative approach combining fluorescent and super-resolution optical photothermal infrared (O-PTIR) imaging. We first show that hybrid α-Syn-Tau 0N3R pre-formed fibrils (PFFs) form more amyloid-rich structures than α-Syn or a-S

Synucleinopathies (e.g. Parkinson's disease and dementia with Lewy bodies) are neurodegenerative conditions characterized by an accumulation of alpha-synuclein from the prodromal phase. Yet, the pathophysiology is far from being completely understood. We have recently identified the cortical synaptic depletion of eukaryotic elongation factor 1A proteins (EEF1A) at early stages of the disease in a mouse model of synucleinopathy (human alpha-synuclein expressing animals under PDGF promoter specific to various brain tissues, PDGF-hSyn).In order to link EEF1A proteins to synucleinopathy changes, w

Synucleinopathies are a group of neurodegenerative disorders characterized by the accumulation of α-synuclein-rich Lewy pathology within neurons and/or glia. Up to 90% of α-synuclein protein within Lewy pathology is phosphorylated at serine residue 129 (pS129), prompting the development of technologies for measuring α-synuclein phosphorylation as a proxy for pathological burden in these disorders. While several assays can quantify human pS129 α-synuclein in patient brain tissues and biofluids, none cross-react with mouse α-synuclein, which is problematic considering the preponderance of mouse