DNA-like fluorescent oligomers composed of alkynyl beta-D-ribofuranosides bearing pyrene, perylene, and anthracene as a fluorophore were synthesized by solid-phase DNA synthesis. The fluorescent oligomers possess the defined number and order of the fluorophores. In these oligomers, the adjacent fluorophores efficiently interact with each other by hydrophobic interactions in their electronic ground states in a face-to-face fashion. The predominant excimer emissions were observed from not only the homooligomers (pyrene-pyrene and perylene-perylene systems) but also the heterooligomers (pyrene-perylene, pyrene-anthracene, and perylene-anthracene systems) in aqueous media.
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http://dx.doi.org/10.1002/chem.200700559 | DOI Listing |
Alzheimers Dement
December 2024
Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Background: Alzheimer's disease (AD) stands as the predominant form of dementia worldwide. The pathogenesis of AD encompasses elevated brain levels of amyloid-β oligomers (AβOs), recognized as central neurotoxins linked to AD. The accumulation of AβOs is neurotoxic, resulting in detrimental effects such as synapse loss, mitochondrial dysfunction, and impairment of proteostasis mechanisms.
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December 2024
Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
Background: The reduced phagocytosis of amyloid β (Aβ) by microglia is linked to increased cognitive decline in Alzheimer's disease (AD) patients. Previous methods utilized anti-Aβ antibodies and flow cytometry to reveal Aβ surface binding without internalization. This study introduces a "Two-Color Fluorescent Reporting System" to overcome limitations, allowing differentiation between intra- and extracellular Aβ.
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December 2024
University of Virginia, Charlottesville, VA, USA.
Background: Tau phosphorylated at threonine-217 (tau), which can be measured in plasma and CSF using antibodies, is one of the most promising early biomarkers for Alzheimer's disease (AD). Little was known, however, about the cellular and subcellular distributions of tau, how those levels change during disease progression, the factor(s) that provoke tau accumulation, or functional consequences of tau phosphorylation at T217. This study addressed all of those issues.
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December 2024
VA Puget Sound GRECC, Seattle, WA, USA.
Background: Alzheimer's disease (AD) is the leading cause of dementia and one of the most devastating neurodegenerative diseases. In the last decades, a large proportion of AD patients have been described as having aberrant accumulation of TDP-43 protein, a well-established driver of neurodegeneration. This TDP-43 proteinopathy in AD can co-occur in neurons with the main hallmarks of the disease, toxic amyloid oligomers and neurofibrillary tangles containing hyperphosphorylated Tau, and correlates with rapid progression and worse prognosis.
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December 2024
University of Toronto, Toronto, ON, Canada.
Background: Drug discovery efforts in neurological diseases, such as Alzheimer's disease (AD), have had particularly poor outcomes due to the lack of models that capture the cerebral vasculature. There is an unmet need to develop models that capture the physiological challenge of overcoming the blood-brain barrier (BBB) and impacts of blood flow-induced shear stress. In this work, we use a microfluidic platform to model the cerebral vasculature in familial AD (fAD) using patient-derived brain endothelial-like cells (BECs) and neurons.
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