Exploring the Locales of Cognitive Decline

Abstract: The progressive accumulation of insoluble aggregates of the presynaptic protein alpha synuclein α Syn is a hallmark of neurodegenerative disorders including Parkinson s disease PD Multiple System Atrophy and Dementia with Lewy Bodies commonly referred to as synucleinopathies Despite considerable progress on the structural biology of these aggregates the molecular

Abstract: Conventional methods of measuring affinity are limited by artificial immobilization large sample volumes and homogeneous solutions This protocol describes microfluidic antibody affinity profiling on complex human samples in solution to obtain a fingerprint reflecting both affinity and active concentration of the target protein To illustrate the protocol we analyze the

Abstract: Many efforts targeting amyloid β Aβ plaques for the treatment of Alzheimer s Disease thus far have resulted in failures during clinical trials Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes In this study we mapped the regional and temporal

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A defining characteristic of mammalian prions is their capacity for self sustained propagation Theoretical considerations and experimental evidence suggest that prion propagation is modulated by cell autonomous and non autonomous modifiers Using a hellip

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Mammalian models are essential for brain aging research However the long lifespan and poor amenability to genetic and pharmacological perturbations have hindered the use of mammals for dissecting aging regulatory molecular hellip

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The effectiveness of therapeutic monoclonal antibodies mAbs against variants of the SARS CoV 2 virus is highly variable As target recognition of mAbs relies on tight binding affinity we assessed the affinities hellip

Abstract: The cellular prion protein PrPC mediates the neurotoxicity of prions and other protein aggregates through poorly understood mechanisms Antibody derived ligands against the globular domain of PrPC GDL can also initiate neurotoxicity by inducing an intramolecular R208 H140 hydrogen bond H latch between the α2 α3 and β2 α2 loops

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Background Multiple System Atrophy is a rare neurodegenerative disease with alpha synuclein aggregation in glial cytoplasmic inclusions and either predominant olivopontocerebellar atrophy or striatonigral degeneration leading to dysautonomia parkinsonism and cerebellar hellip

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Although prion infections cause cognitive impairment and neuronal death transcriptional and translational profiling shows progressive derangement within glia but surprisingly little changes within neurons Here we expressed PrPC selectively in hellip

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Deposits of amyloid β Aβ in the brains of rodents can be analysed by invasive intravital microscopy on a submillimetre scale or via whole brain images from modalities lacking the resolution or hellip

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Prion infections cause conformational changes of the cellular prion protein PrPC and lead to progressive neurological impairment Here we show that toxic prion mimetic ligands induce an intramolecular R208 H140 hydrogen bond hellip

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Recent efforts in understanding the course and severity of SARS CoV 2 infections have highlighted both potentially beneficial and detrimental effects of cross reactive antibodies derived from memory immunity Specifically due to a hellip

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An increased incidence of chilblains has been observed during the severe acute respiratory syndrome coronavirus 2 SARS CoV 2 pandemic and attributed to viral infection Direct evidence of this relationship has been hellip

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The clinical outcome of SARS CoV 2 infections which can range from asymptomatic to lethal is crucially shaped by the concentration of antiviral antibodies and by their affinity to their targets However hellip

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Despite being caused by a single protein prion diseases are strikingly heterogenous Individual prion variants known as strains possess distinct biochemical properties form aggregates with characteristic morphologies and preferentially seed hellip

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Antiphospholipid antibodies aPL assumed to cause antiphospholipid syndrome APS are notorious for their heterogeneity in targeting phospholipids and phospholipid binding proteins The persistent presence of Lupus anticoagulant and or aPL against cardiolipin hellip

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The misfolding and aggregation of the human prion protein PrP is associated with transmissible spongiform encephalopathies TSEs Intermediate conformations forming during the conversion of the cellular form of PrP into hellip

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The cellular prion protein PrPC is necessary for prion replication and its reduction greatly increases life expectancy in animal models of prion infection Hence the factors controlling the levels of hellip

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While the initial pathology of Parkinson s disease and other α synucleinopathies is often confined to circumscribed brain regions it can spread and progressively affect adjacent and distant brain locales This process hellip

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Brain matter vacuolation is a defining trait of all prion diseases yet its cause is unknown Here we report that prion infection and prion mimetic antibodies deplete the phosphoinositide kinase PIKfyve which controls hellip

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Neuropathological and experimental evidence suggests that the cell to cell transfer of α synuclein has an important role in the pathogenesis of Parkinson 8217 s disease PD However the mechanism underlying this phenomenon is not hellip

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Abstract The progression of prion diseases is accompanied by the accumulation of prions in the brain Ablation of microglia enhances prion accumulation and accelerates disease progression suggesting that microglia play hellip

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Prion immunotherapy may hold great potential but antibodies against certain PrP epitopes can be neurotoxic Here we identified > 6 000 PrP binding antibodies in a synthetic human Fab phage display library 49 of hellip

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Prion diseases are caused by PrPSc a self replicating pathologically misfolded protein that exerts toxicity predominantly in the brain The administration of PrPSc causes a robust reproducible and specific disease manifestation hellip

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Transmission of prion infectivity to susceptible murine cell lines has simplified prion titration assays and has greatly reduced the need for animal experimentation However murine cell models suffer from technical hellip

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The clinical course of prion diseases is accurately predictable despite long latency periods suggesting that prion pathogenesis is driven by precisely timed molecular events We constructed a searchable genome wide atlas hellip

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Microglia play vital roles in the health and diseases of the central nervous system Loss of microglia homeostatic state is a key feature of brain aging and neurodegeneration However the hellip

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Light sheet microscopy is an ideal technique for imaging large cleared samples however the community is still lacking instruments capable of producing volumetric images of centimeter sized cleared samples with near isotropic resolution hellip

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Alzheimer 8217 s disease AD Parkinson 8217 s disease PD and prion diseases such as Creutzfeldt Jakob disease attack different parts of the central nervous system CNS and elicit distinct symptoms yet they share many hellip

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SARM1 sterile α and HEAT armadillo motif containing protein is a member of the MyD88 myeloid differentiation primary response gene 88 family which mediates innate immune responses Because inactivation of SARM1 prevents hellip