Crucial roles of UCH-L1 on insulin-producing cells and carbohydrate metabolism in Drosophila melanogaster model.

Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a highly expressed protein in ß cells and has been implicated in ß cells' viability and function, however, the role of UCH-L1 in ß cells remains unclear. Herein, we examined the functions of UCH-L1 in ß cells by utilizing the Drosophila melanogaster model. Our results showed that specific knockdown of dUCH (D.melanogaster homolog of UCH-L1) in Drosophila Insulin-producing cells (D.melanogaster homolog of ß cells) induced mitochondria fusion, IPCs death/degeneration, interfered with DILP2 secretion, and triggered the rise of glycogen storage and body weight. Strikingly, the impairment in IPCs cellular activities can be rescued by vitamin C- a strong antioxidant compound, which suggested the relationship between knockdown dUCH and oxidative stress in IPCs; and the potential of this model in screening compounds for ß cells function moderation. Since carbohydrate metabolism is an important function of beta cells, we continued to examine the ability to regulate carbohydrate metabolism of knockdown dUCH flies. Our results showed that knockdown dUCH caused the decline of IPCs number under a high-sucrose diet, which finally led to metabolic and physiological disturbances, including total lipid rise, glycogen storage reduction, circulating carbohydrate increase, and weight loss. These symptoms could be early indications of metabolic disorders, particularly ß cell dysfunction-related diseases. Taken together, our results indicate that dUCH is essential in the viability and functions of IPCs through the regulation of carbohydrate metabolism in the Drosophila model.

Rumdul (Sphaerocoryne affinis) Antioxidant Activity and Its Potential for Parkinson's Disease Treatment.

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by progressive deterioration of motor function and loss of dopaminergic neurons in the substantia nigra. Although PD is more common in people over 60 years old, people with young-onset PD tend to increase recently. Up to now, there is no cure for PD; therapies mainly focus on reducing symptoms and improving patient quality of life. Thus, the requirement of exploring new medications is needed. There is a strong relationship between oxidative stress and PD. Therefore, antioxidant compounds have been considered as a novel therapy for PD. In this study, we indicated a new potential candidate for PD treatment, rumdul fruit (Sphaerocoryne affinis-a member of the Annonaceae family), due to evaluating its activities on the fly model of Parkinson. Our experimental results showed that rumdul fruit water extract (RFWE) has a strong antioxidant capacity with IC50 value in DPPH assay which was 85.62 ± 1.05 µg/mL. The use of RFWE at concentrations of 3, 6, and 12 mg/mL could strongly ameliorate the locomotor disabilities and dopaminergic neuron degeneration. Although the RFWE at high concentrations like 12 mg/mL and 18 mg/mL could induce some side effects on fly development and viability, our data strongly demonstrated that RFWE effectively rescued PD phenotypes on the fly model. Although component in the plant extract, as well as the molecular mechanism helping to recover the phenotype, has not been elucidated yet, the research contributed strong scientific evidence for further research on applying rumdul as a novel natural source for PD treatment.

Evaluating Dose- and Time-Dependent Effects of Vitamin C Treatment on a Parkinson's Disease Fly Model.

Parkinson's disease (PD) is a common neurodegenerative disorder and characterized by progressive locomotive defects and loss of dopaminergic neurons (DA neuron). Currently, there is no potent therapy to cure PD, and the medications merely support to control the symptoms. It is difficult to develop an effective treatment, since the PD onset mechanism of PD is still unclear. Oxidative stress is considered as a major cause of neurodegenerative diseases, and there is increasing evidence for the association between PD and oxidative stress. Therefore, antioxidant treatment may be a promising therapy for PD. Drosophila with knockdown of dUCH, a homolog of UCH-L1 which is a PD-related gene, exhibited PD-like phenotypes including progressive locomotive impairments and DA neuron degeneration. Moreover, knockdown of dUCH led to elevated level of ROS. Thus, dUCH knockdown flies can be used as a model for screening of potential antioxidants for treating PD. Previous studies demonstrated that curcumin at 1 mM and vitamin C at 0.5 mM could improve PD-like phenotypes induced by this knockdown. With the purpose of further investigating the efficiency of vitamin C in PD treatment, we used dUCH knockdown Drosophila model to examine the dose- and time-dependent effects of vitamin C on PD-like phenotypes. The results showed that although vitamin C exerted neuroprotective effects, high doses of vitamin C and long-term treatment with this antioxidant also resulted in side effects on physiology. It is suggested that dose-dependent effects of vitamin C should be considered when used for treating PD.