0000000000429575

AUTHOR

Wilfried Nietfeld

showing 2 related works from this author

The Anti-amyloid Compound DO1 Decreases Plaque Pathology and Neuroinflammation-Related Expression Changes in 5xFAD Transgenic Mice

2018

Self-propagating amyloid-β (Aβ) aggregates or seeds possibly drive pathogenesis of Alzheimer's disease (AD). Small molecules targeting such structures might act therapeutically in vivo. Here, a fluorescence polarization assay was established that enables the detection of compound effects on both seeded and spontaneous Aβ42 aggregation. In a focused screen of anti-amyloid compounds, we identified Disperse Orange 1 (DO1) ([4-((4-nitrophenyl)diazenyl)-N-phenylaniline]), a small molecule that potently delays both seeded and non-seeded Aβ42 polymerization at substoichiometric concentrations. Mechanistic studies revealed that DO1 disrupts preformed fibrillar assemblies of synthetic Aβ42 peptides …

MaleGenetically modified mouse1303 BiochemistryAmyloid10017 Institute of AnatomyClinical BiochemistryMice TransgenicPlaque Amyloid610 Medicine & healthBiologyProtein aggregation1308 Clinical Biochemistry01 natural sciencesBiochemistryPolymerizationPathogenesisMiceProtein AggregatesStructure-Activity RelationshipAlzheimer DiseaseGene expressionDrug Discovery1312 Molecular BiologyAnimalsColoring AgentsMolecular BiologyNeuroinflammationInflammationPharmacologyAmyloid beta-PeptidesDose-Response Relationship DrugMolecular Structure010405 organic chemistry3002 Drug DiscoveryBrainSmall moleculeMolecular medicine0104 chemical sciencesCell biologyMice Inbred C57BL3004 Pharmacology10036 Medical Clinic1313 Molecular Medicine570 Life sciences; biologyMolecular MedicineFemaleAzo Compounds
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RNA Sequencing of Human Peripheral Blood Cells Indicates Upregulation of Immune-Related Genes in Huntington's Disease

2020

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD ca…

inflammationHuntington's diseaseRNA-Seqdifferential gene expressiondisease markerslcsh:Neurology. Diseases of the nervous systemlcsh:RC346-429Frontiers in Neurology
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