Mn(II) Quinoline Complex (4QMn) Restores Proteostasis and Reduces Toxicity in Experimental Models of Huntington’s Disease
Mn(II) Quinoline Complex (4QMn) Restores Proteostasis and Reduces Toxicity in Experimental Models of Huntington’s Disease
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder, of the so-called minority diseases, due to its low prevalence. It is caused by an abnormally long track of glutamines (polyQs) in mutant huntingtin (mHtt), which makes the protein toxic and prone to aggregation. Many pathways of clearance of badly-folded proteins are disrupted in neurons of patients with HD. In this work, we show that one Mn(II) quinone complex (4QMn), designed to work as an artificial superoxide dismutase, is able to activate both the ubiquitin-proteasome system and the autophagy pathway in vitro and in vivo models of HD. Activation of these pathways degrades mHtt and other protein-containing polyQs, which restores proteostasis in these models. Hence, we propose 4QMn as a potential drug to develop a therapy to treat HD.
An antioxidant boehmite amino-nanozyme able to disaggregate Huntington’s inclusion bodies
An antioxidant boehmite amino-nanozyme able to disaggregate Huntington’s inclusion bodies
A novel amino-nanozyme, based on boehmite nanoparticles (BNPs) functionalised with a tetra-azapyridinophane (L1), has been designed to undermine some of the key issues underlying Huntington disease. L1 forms Cu2+ complexes with a striking SOD activity, while when grafted to the BNPs displays mitoROS scavenging properties and ability to disaggregate mutant huntingtin deposits in cells.
The Embryonic Key Pluripotent Factor NANOG Mediates Glioblastoma Cell Migration via the SDF1/CXCR4 Pathway
The Embryonic Key Pluripotent Factor NANOG Mediates Glioblastoma Cell Migration via the SDF1/CXCR4 Pathway
NANOG is a key transcription factor required for maintaining pluripotency of embryonic stem cells. Elevated NANOG expression levels have been reported in many types of human cancers, including lung, oral, prostate, stomach, breast, and brain. Several studies reported the correlation between NANOG expression and tumor metastasis, revealing itself as a powerful biomarker of poor prognosis.
Undetectable viral RNA from SARS-CoV-2 in endometrial biopsies from women with COVID-19: a preliminary study
Undetectable viral RNA from SARS-CoV-2 in endometrial biopsies from women with COVID-19: a preliminary study
From the time of its first appearance, the
novelty of the SARS-CoV-2, which is responsible for COVID-
19, has generated many important questions about its effects
on human health.
SARS-CoV-2 is a single-stranded, enveloped RNA virus that
incorporates 3 types of transmembrane proteins (spike [S],
envelope, and membrane) and a nucleocapsid (N) structural
protein.
Medaka ( Oryzias latipes) Embryo as a Model for the Screening of Compounds That Counteract the Damage Induced by Ultraviolet and High-Energy Visible Light
Medaka ( Oryzias latipes) Embryo as a Model for the Screening of Compounds That Counteract the Damage Induced by Ultraviolet and High-Energy Visible Light
Continuous overexposure to sunlight increases its harmful effects on the skin. For this reason, there is a growing need to characterize economic models more representative of the negative effects and counteracting responses that irradiation causes on human skin. These models will serve for the screening of protective compounds against damage caused by ultraviolet (UV) and high energy visible light (HEV). Therefore, two common in vitro models employed for sunlight irradiation studies, namely human keratinocyte HaCat culture and reconstructed human epidermis (RHE), were compared with the medaka fish embryo model, traditionally used in other scientific disciplines. Using suberythemal doses of UVA and HEV to determine the level of Reactive Oxygen Species (ROS) generation and thymine dimers formed by UVB, we show that medaka embryo responds with a lower damage level, more comparable to human skin, than the other two models, probably due to the protective mechanisms that work in a complete organism. In the same way, the protective effects of antioxidant compounds have the greatest effect on medaka embryos. Taken together, these findings suggest that medaka embryos would be a good alternative in vitro model for sunlight effect studies, and for the screening of molecules with counteracting capacity against the damage caused by UV and HEV.
Use of Medaka Fish as Vertebrate Model to Study the Effect of Cocoa Polyphenols in the Resistance to Oxidative Stress and Life Span Extension
Use of Medaka Fish as Vertebrate Model to Study the Effect of Cocoa Polyphenols in the Resistance to Oxidative Stress and Life Span Extension
Oxidative stress (OS) can induce cell apoptosis and thus plays an important role in aging. Antioxidant foods protect tissues from OS and contribute to a healthier lifestyle. In this study, we described the used of medaka embryos (Oryzias latipes) to study the putative antioxidant capacity of dietary cocoa extract in vertebrates. A polyphenol-enriched cocoa extract regulated the expression of several genes implicated in OS, thereby protecting fish embryos from induced OS. The cocoa extract activated superoxide dismutase enzyme activity in embryos and adult fish tissues, suggesting a common mechanism for protection during embryonic development and adulthood. Furthermore, long-term feeding of the cocoa extract increased fish life span. Our study demonstrates that the polyphenol-enriched cocoa extract decreases OS and extends life span in medaka fish, validating the use of medaka embryos as an economical platform to screen the antioxidant capacity of food compounds.
Mn(II) complexes of scorpiand-like ligands. A model for the MnSOD active centre with high in vitro and in vivo activity
Mn(II) complexes of scorpiand-like ligands. A model for the MnSOD active centre with high in vitro and in vivo activity
Manganese complexes of polyamines consisting of an aza-pyridinophane macrocyclic core functionalised with side chains containing quinoline or pyridine units have been characterised by a variety of solution techniques and single crystal x-ray diffraction. Some of these compounds have proved to display interesting antioxidant capabilities in vitro and in vivo in prokaryotic (bacteria) and eukaryotic (yeast and fish embryo) organisms. In particular, the Mn complex of the ligand containing a 4-quinoline group in its side arm which, as it happens in the MnSOD enzymes, has a water molecule coordinated to the metal ion that shows the lowest toxicity and highest functional efficiency both in vitro and in vivo.