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Background: DYRK1A overexpression, common in neurodegenerative diseases like Alzheimer's (AD), contributes to neurofibrillary tangles via Tau protein hyperphosphorylation and amyloid plaque formation, key AD hallmarks. Therefore, DYRK1A has been regarded as a novel target for neurodegenerative diseases. However, developing DYRK1A selective inhibitors has been a difficult challenge due to the highly conserved ATP-binding site of protein kinases, particularly among the CMGC family.
View Article and Find Full Text PDFBackground: Progranulin (GRN) plays a critical role in familial frontotemporal dementia (fFTD), where GRN haploinsufficiency leads to reduction in PGRN levels in the brain, resulting in degeneration of neurons in the frontal lobe of brain responsible for personality, language, and behavior. FTD is the most common dementia in people under 60. Sortilin (Sort1), expressed by neurons, endocytoses, and delivers PGRN rapidly to lysosomes for degradation.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The TaRget Enablement to Accelerate Therapy Development of Alzheimer's Disease (TREAT-AD) Centers are dedicated to identifying and validating targets from the NIH Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD). The centers develop Target Enabling Packages (TEPs) to explore new therapeutic target hypotheses, moving beyond the traditional focus on amyloid or tau pathologies. In accordance with open science principles, data, methods, and tools are freely shared with the research community via an open-access platform, the AD Knowledge Portal.
View Article and Find Full Text PDFIndirect Detection of the Protons in and around Biradicals and their Mechanistic Role in MAS-DNP.
J Phys Chem Lett
January 2025
National High Magnetic Field Laboratory, Florida State University, 1800 E. Paul Dirac Dr, Tallahassee, Florida 32310, United States.
The contribution of protons in or near biradical polarizing agents in Dynamic Nuclear Polarization (DNP) has recently been under scrutiny. Results from selective deuteration and simulations have previously suggested that the role of protons in the biradical molecule depends on the strength of the electron-electron coupling. Here we use the cross effect DNP mechanism to identify and acquire H solid-state NMR spectra of the protons that contribute to propagation of the hyperpolarization, via an experimental approach dubbed Nuclear-Nuclear Double Resonance (NUDOR).
View Article and Find Full Text PDFPhotocurrent Generation by Plant Light-Harvesting Complexes is Enhanced by Lipid-Linked Chromophores in a Self-Assembled Lipid Membrane.
J Phys Chem B
January 2025
Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan.
The light-harvesting pigment-protein complex II (LHCII) from plants can be used as a component for biohybrid photovoltaic devices, acting as a photosensitizer to increase the photocurrent generated when devices are illuminated with sunlight. LHCII is effective at photon absorption in the red and blue regions of the visible spectrum, however, it has low absorption in the green region (550-650 nm). Previous studies have shown that synthetic chromophores can be used to fill this spectral gap and transfer additional energy to LHCII, but it was uncertain whether this would translate into an improved performance for photovoltaics.
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