Exploring the Efficient Natural Products for the Therapy of Parkinson's Disease via Drosophila Melanogaster (Fruit Fly) Models.

Parkinson's disease (PD) is a severe neurodegenerative disorder, partly attributed to mutations, environmental toxins, oxidative stress, abnormal protein aggregation, and mitochondrial dysfunction. However, the precise pathogenesis of PD and its treatment strategy still require investigation. Fortunately, natural products have demonstrated potential as therapeutic agents for alleviating PD symptoms due to their neuroprotective properties. To identify promising lead compounds from herbal medicines' natural products for PD management and understand their modes of action, suitable animal models are necessary. Drosophila melanogaster (fruit fly) serves as an essential model for studying genetic and cellular pathways in complex biological processes. Diverse Drosophila PD models have been extensively utilized in PD research, particularly for discovering neuroprotective natural products. This review emphasizes the research progress of natural products in PD using the fruit fly PD model, offering valuable insights into utilizing invertebrate models for developing novel anti-PD drugs.

Insect cuticle and insecticide development.

Insecticide resistance poses a significant challenge, diminishing the effectiveness of chemical insecticides. To address this global concern, the development of novel and efficient pest management technologies based on chemical insecticides is an ongoing necessity. The insect cuticle, a highly complex and continuously renewing organ, plays a crucial role in this context. On one hand, as the most vital structure, it serves as a suitable target for insecticides. On the other hand, it acts as the outermost barrier, isolating the insect's inner organs from the environment, and thus offering resistance to contact with insecticides, preventing their entry into insect bodies. Our work focuses on key targets concerning cuticle formation and the interaction between the cuticle and contact insecticides. Deeper studying insect cuticles and understanding their structure-function relationship, formation process, and regulatory mechanisms during cuticle development, as well as investigating insecticide resistance related to the barrier properties of insect cuticles, are promising strategies not only for developing novel insecticides but also for discovering general synergists for contact insecticides. With this comprehensive review, we hope to contribute valuable insights into the development of effective pest management solutions and the mitigation of insecticide resistance.

Anaerobic purinolytic enzymes enable dietary purine clearance by engineered gut bacteria.

Uric acid, the end product of purine degradation, causes hyperuricemia and gout, afflicting hundreds of millions of people. The debilitating effects of gout are exacerbated by dietary purine intake, and thus a potential therapeutic strategy is to enhance purine degradation in the gut microbiome. Aerobic purine degradation involves oxidative dearomatization of uric acid catalyzed by the O2-dependent uricase. The enzymes involved in purine degradation in strictly anaerobic bacteria remain unknown. Here we report the identification and characterization of these enzymes, which include four hydrolases belonging to different enzyme families, and a prenyl-flavin mononucleotide-dependent decarboxylase. Introduction of the first two hydrolases to Escherichia coli Nissle 1917 enabled its anaerobic growth on xanthine as the sole nitrogen source. Oral supplementation of these engineered probiotics ameliorated hyperuricemia in a Drosophila melanogaster model, including the formation of renal uric acid stones and a shortened lifespan, providing a route toward the development of purinolytic probiotics.

The fruit fly kidney stone models and their application in drug development.

Kidney stone disease is a global problem affecting about 12% of the world population. Novel treatments to control this disease have a huge demand. Here we argue that the fruit fly, as an emerging kidney stone model, can provide a platform for the discovery of new drugs. The renal system of fruit fly (Malpighian tubules) is similar to the mammalian renal tubules in both function and structure. Different fruit fly models for different types of kidney stones including calcium oxalate (CaOx) stones, xanthine stones, uric acid stone, and calcium phosphate (CaP) stones have been successfully established through dietary or genetic approaches in the last ten years, notably improved our understanding of the formation mechanisms of kidney stone diseases. The fruit fly CaOx stones model, which is mediated by treatment with dietary lithogenic agents, is also one of the most potential models for drug development. Various potential antilithogenic agents have been identified using this model, including new chemical compounds and medicinal plants. The fruit fly kidney stone models also afford opportunities to study the therapeutic mechanism of these drugs in deeper.