Friedreich ataxia (FRDA) is an inherited neurodegenerative disease caused by frataxin (FXN) deficiency. The nervous system and heart are the most severely affected tissues. However, highly mitochondria-dependent tissues, such as kidney and liver, are not obviously affected, although the abundance of FXN is normally high in these tissues. In this study we have revealed two novel FXN isoforms (II and III), which are specifically expressed in affected cerebellum and heart tissues, respectively, and are functional in vitro and in vivo. Increasing the abundance of the heart-specific isoform III significantly increased the mitochondrial aconitase activity, while over-expression of the cerebellum-specific isoform II protected against oxidative damage of Fe-S cluster-containing aconitase. Further, we observed that the protein level of isoform III decreased in FRDA patient heart, while the mRNA level of isoform II decreased more in FRDA patient cerebellum compared to total FXN mRNA. Our novel findings are highly relevant to understanding the mechanism of tissue-specific pathology in FRDA.
Alzheimer's disease (AD) is the most common dementia and the trigger of its pathological cascade is widely believed to be the overproduction and accumulation of β-amyloid protein (Aβ) in the affected brain. However, effective AD remedies are still anxiously awaited. Recent evidence suggests that curcumin may be a potential agent for AD treatment. In this study, we used 5×FAD transgenic mice as an AD model to investigate the effects of curcumin on AD. Our results showed that curcumin administration (150 or 300 mg/kg/day, intragastrically, for 60 days) dramatically reduced Aβ production by downregulating BACE1 expression, preventing synaptic degradation, and improving spatial learning and memory impairment of 5×FAD mice. These findings suggest that curcumin is a potential candidate for AD treatment.
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