Dendrimer-Conjugated nSMase2 Inhibitor Reduces Tau Propagation in Mice
Pharmaceutics, 2022 Alzheimer’s disease (AD) is characterized by the progressive accumulation of amyloid-β and hyperphosphorylated tau (pTau), which can spread throughout the brain via extracellular vesicles (EVs).
Carolyn Tallon +14 more
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Microglial-Targeted nSMase2 Inhibitor Fails to Reduce Tau Propagation in PS19 Mice
Pharmaceutics, 2023 The progression of Alzheimer’s disease (AD) correlates with the propagation of hyperphosphorylated tau (pTau) from the entorhinal cortex to the hippocampus and neocortex.
Meixiang Huang +13 more
doaj +4 more sources
Inhibition of nSMase2 Reduces the Transfer of Oligomeric α-Synuclein Irrespective of Hypoxia [PDF]
Frontiers in Molecular Neuroscience, 2019 Recently, extracellular vesicles (EVs), such as exosomes, have been proposed to play an influential role in the cell-to-cell spread of neurodegenerative diseases, including the intercellular transmission of α-synuclein (α-syn). However, the regulation of
Valerie Sackmann +12 more
doaj +6 more sources
Pharmacological inhibition of nSMase2 reduces brain exosome release and α-synuclein pathology in a Parkinson’s disease model [PDF]
Molecular Brain, 2021 Aim We have previously reported that cambinol (DDL-112), a known inhibitor of neutral sphingomyelinase-2 (nSMase2), suppressed extracellular vesicle (EV)/exosome production in vitro in a cell model and reduced tau seed propagation.
Chunni Zhu +12 more
doaj +7 more sources
Cambinol, a novel inhibitor of neutral sphingomyelinase 2 shows neuroprotective properties. [PDF]
PLoS ONE, 2015 Ceramide is a bioactive lipid that plays an important role in stress responses leading to apoptosis, cell growth arrest and differentiation. Ceramide production is due in part to sphingomyelin hydrolysis by sphingomyelinases.
Mariana Figuera-Losada +11 more
doaj +3 more sources
Ligand‑Based Virtual Screening Discovery of Thienopyrimidinone Derivatives as Allosteric nSMase2 Modulators and Antivirals Against West Nile Virus. [PDF]
ChemMedChemOrthoflaviviruses such as West Nile virus (WNV), Zika virus (ZIKV), or dengue virus (DENV) represent a growing global health threat, with millions of annual infections and no approved antiviral therapies.
Álvarez-Fernández H +6 more
europepmc +3 more sources
Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP
Journal of Medicinal Chemistry, 2022 Extracellular vesicles (EVs) can carry pathological cargo and play an active role in disease progression. Neutral sphingomyelinase-2 (nSMase2) is a critical regulator of EV biogenesis, and its inhibition has shown protective effects in multiple disease ...
Norman Haughey (5733533) +11 more
core +4 more sources
The nSMase2/Smpd3 gene modulates the severity of muscular dystrophy and the emotional stress response in mdx mice [PDF]
BMC Medicine, 2020 Background Duchenne muscular dystrophy (DMD) is a progressive, degenerative muscular disorder and cognitive dysfunction caused by mutations in the dystrophin gene.
Yasunari Matsuzaka +15 more
doaj +3 more sources
Stress-induced sphingolipid signaling: role of type-2 neutral sphingomyelinase in murine cell apoptosis and proliferation. [PDF]
PLoS ONE, 2010 BACKGROUND:Sphingomyelin hydrolysis in response to stress-inducing agents, and subsequent ceramide generation, are implicated in various cellular responses, including apoptosis, inflammation and proliferation, depending on the nature of the different ...
Raphael Devillard +8 more
doaj +2 more sources
The expression of PHOSPHO1, nSMase2 and TNAP is coordinately regulated by continuous PTH exposure in mineralising osteoblast cultures [PDF]
Calcified Tissue International, 2016 Sustained exposure to high levels of parathyroid hormone (PTH), as observed in hyperparathyroidism, are catabolic to bone. The increase in the RANKL/OPG ratio in response to continuous PTH, resulting in increased osteoclastogenesis is well established ...
Farquharson, C +17 more
core +6 more sources