The relationship between oxidative stress and neurodegenerative diseases has been extensively examined, and antioxidants are considered to be a promising approach for decelerating disease progression. Parkinson's disease (PD) is a common neurodegenerative disorder and affects 1% of the population over 60 years of age. A complex combination of genetic and environmental factors contributes to the pathogenesis of PD. However, since the onset mechanisms of PD have not yet been elucidated in detail, difficulties are associated with developing effective treatments. Curcumin has been reported to have neuroprotective properties in PD models induced by neurotoxins or genetic factors such as α-synuclein, PINK1, DJ-1, and LRRK2. In the present study, we investigated the effects of curcumin in a novel Drosophila model of PD with knockdown of dUCH, a homolog of human UCH-L1. We found that dopaminergic neuron-specific knockdown of dUCH caused impaired movement and the loss of dopaminergic neurons. Furthermore, the knockdown of dUCH induced oxidative stress while curcumin decreased the ROS level induced by this knockdown. In addition, dUCH knockdown flies treated with curcumin had improved locomotive abilities and less severe neurodegeneration. Taken together, with studies on other PD models, these results strongly suggest that treatments with curcumin are an appropriate therapy for PD related to oxidative stress.
KGF (Keratinocyte Growth Factor), also known as FGF7, is a potent mitogen for different types of epithelial cells, which regulates migration and differentiation of these cells and protects them from various insults under stress conditions. KGF is produced by mesenchymal cells and exerts its biological effects via binding to its high-affinity receptor, a splice variant of FGF receptor 2 (FGFR2-IIIb), which is expressed by various types of epithelial cells, including epidermal keratinocytes, intestinal epithelial cells, and hepatocytes. This expression pattern of KGF and its receptor suggests that KGF acts predominantly in a paracrine manner. After acute injury, in various tissues--including the skin, the bladder as well as in chronically injured tissue--KGF expression is strongly up-regulated. This up-regulation is likely to be important for the healing of injured epithelia. In addition, KGF could also exert a protective effect on these cells. There are many researches have been underway to identify clinical applications for KGF. Specifically, KGF is currently being evaluated in clinical trials sponsored by Amgen (Thousand Oaks, CA) to test its ability to ameliorate severe oral mucositis (OM) that results from cancer chemoradiotherapy. In this paper, we provide an overview of the knowledge on molecular properties, biological functions and the recent findings on clinical application of KGF.
Parkinson’s disease (PD), which is characterized by the decreased motor function and the loss of dopaminergic neurons, is a common neurodegenerative disorder in elders. There have been numerous in vitro and in vivo models developed to study mechanisms of PD and screen potential drug. Recently, dUCH-knockdown Drosophila model has been established and showed potential for screening antioxidants for PD treatment. The dUCH-knockdown Drosophila model of PD mimics most of main PD pathologies such as dopaminergic neurons degeneration, locomotor dysfunction, and shortage of dopamine in the brain. Common purslane (Portulaca oleracea L.) is a nutritious vegetable containing a variety of antioxidants, levodopa, and dopamine, a neurotransmitter closely related to PD. Purslane has been reported to exert neuroprotective effects against several neurotoxins including rotenone and 6-OHDA in PD models. However, the recent data have not provided sufficient evidence for using purslane to treat PD or decelerate disease progression. Therefore, in this study, we utilized dUCH-knockdown fly to evaluate the capacity of purslane extracts for PD treatment. The results showed that purslane extracts improved locomotor ability in the larval stage and decelerated disease progression in the adult stage. Additionally, purslane extracts also reduced dopaminergic neuron degeneration. Taken together, our data strongly demonstrated that purslane extracts effectively rescued PD-like phenotypes in the fly model. This result contributed a foundation for further study on the application of purslane in PD treatment.
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