![]() ![]() ![]() Abnormal iron metabolism and mitochondrial dysfunction are the pathologic and cytologic basis of the disease, and the cerebellum, heart, and spine are the main affected tissues. Deficiency of Fe-S compromises mitochondrial quality, including its disorganized cristae, less cristae, and less mitochondrial number, resulting in mitochondrial dysfunction (reviewed in ). The GAA expansion mutation leads to reduction of the transcription of frataxin, a highly conserved nuclear-encoded mitochondrial protein involved in the biosynthesis of iron sulfur cluster (Fe-S). Graphical Abstractįriedrich's ataxia (FRDA) is a single-gene inherited recessive neurodegenerative disease caused by expansion of triplet nucleotide GAA repeats in the first intron of the frataxin ( FXN) gene, characterized by progressive cerebellar and sensory ataxia. These data encourage us to propose that NPs are a promising therapeutic compound in the application of FRDA disease. ![]() NPs showed a significant advantage in neuron and myocardial function, thereby improving FRDA mouse behavior scores. NPs not only removed iron from the heart and diminished oxidative stress in general but also potentiate iron-sulfur cluster biogenesis, which compensates FXN deficiency to improve the morphology and function of mitochondria. Here, we synthesized slow-release nanoparticles (NPs) by loading curcumin (Cur) into silk fibroin (SF) to form NPs with an average size of 150 nm NPs), which exhibited satisfactory therapeutic effects on the improvement of FRDA manifestation in lymphoblasts (1 μM) derived from FRDA patients and in YG8R mice (150 mg/kg/5 days). However, its limitation is its poor water solubility and permeability. Curcumin is proposed harboring excellent ability to resist oxidative stress through Nrf2 activation and its newly found ability to chelate iron. To date, there is no effective therapy to treat this condition. This disease is caused by frataxin ( FXN) mutation, which reduces FXN expression and impairs iron sulfur cluster biogenesis. cinerea.Abnormal iron metabolism, mitochondrial dysfunction and the derived oxidative damage are the main pathogeneses of Friedrich's ataxia (FRDA), a single-gene inherited recessive neurodegenerative disease characterized by progressive cerebellar and sensory ataxia. The results suggested that Cu-NPs in combination with conventional fungicides can provide the means for an environmentally safe, sustainable resistance management strategy by reducing fungicide use and combating resistance against B. Furthermore, the observed cross sensitivity and antagonistic action between Cu-NPs and NaCl also provided evidence for copper ions contribution to the fungitoxic action of Cu-NPs. A synergistic profile was observed between Cu-NPs and fluazinam (FM) - an oxidative phosphorylation inhibitor - in all isolates regardless of resistance phenotype, suggesting that ATP metabolism could be involved in the mode of action of Cu-NPs. No correlation between Cu(OH)2 and Cu-NPs sensitivity was found, indicating that different mechanisms govern the fungitoxic activity between nano and bulk counterparts. A positive correlation was observed between TM and TM + Cu-NPs treatments, suggesting that an increased TM availability in the target site could be related with the observed additive/synergistic action. An additive/synergistic effect was observed between Cu-NPs and TM in the case of BEN-S isolates both in vitro and when applied in apple fruit. ![]() Cu-NPs were equally effective against sensitive and resistant isolates. cinerea isolates highly resistant to benzimidazoles (BEN-R), thiophanare methyl (TM), and carbendazim, bearing the E198A resistance mutation in the β-tubulin gene, and four isolates highly resistant to the QoI pyraclostrobin (PYR-R) with a G143A mutation in the cytb gene. Sensitivity screening in vitro revealed two fungicide resistance phenotypes, resulting from target site mutations. In this study, the potential of copper nanoparticles (Cu-NPs) to suppress 15 Botrytis cinerea isolates, which are sensitive or resistant to fungicides, alone or in combination with conventional fungicides, was tested in vitro and in vivo. ![]()
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