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http://dx.doi.org/10.1212/WNL.0b013e31825dcdac | DOI Listing |
Background: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Alzheimers Dement
December 2024
MRC Protein Phosphorylation and Ubiquitylation Unit, Dundee, Scotland, United Kingdom.
Background: Accumulation of misfolded a-synuclein protein in intracellular inclusion bodies of dopaminergic neurons underlies the pathogenesis of synucleinopathies, which include Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). Therefore, clearance of misfolded α-synuclein from dopaminergic neurons could in principle offer a an approach for modifying synucleinopathies, which currently remain untreatable.
Method: In this study, we employ the Affinity-directed PROtein Missile (AdPROM) system consisting of the substrate receptor of the CUL2-E3 ligase complex VHL and a nanobody selectively recognising the human α-synuclein protein RESULT: We demonstrate targeted degradation of endogenous α-synuclein from human cell lines with exquisite selectivity.
Background: Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by the accumulation of neurofibrillary tangles (NFTs) which consist primarily of hyperphosphorylated tau protein. Abnormal phosphorylated tau has been considered as a pathogenic species that impairs cellular function and propagates from neuron to neuron. AD affects millions of people around the world, however, there's no effective drug that can prevent or cure the disease to date.
View Article and Find Full Text PDFCell Commun Signal
January 2025
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Background: Staphylococcus aureus, a known contributor to non-healing wounds, releases vesicles (SAVs) that influence the delicate balance of host-pathogen interactions. Efferocytosis, a process by which macrophages clear apoptotic cells, plays a key role in successful wound healing. However, the precise impact of SAVs on wound repair and efferocytosis remains unknown.
View Article and Find Full Text PDFCell Death Differ
January 2025
Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.
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