Forest trees are a major source of biogenic volatile organic compounds (BVOCs). Terpenes and terpenoids are known as the main BVOCs of forest aerosols. These compounds have been shown to display a broad range of biological activities in various human disease models, thus implying that forest aerosols containing these compounds may be related to beneficial effects of forest bathing. In this review, we surveyed studies analyzing BVOCs and selected the most abundant 23 terpenes and terpenoids emitted in forested areas of the Northern Hemisphere, which were reported to display anti-inflammatory activities. We categorized anti-inflammatory processes related to the functions of these compounds into six groups and summarized their molecular mechanisms of action. Finally, among the major 23 compounds, we examined the therapeutic potentials of 12 compounds known to be effective against respiratory inflammation, atopic dermatitis, arthritis, and neuroinflammation among various inflammatory diseases. In conclusion, the updated studies support the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic agents for treating various inflammatory diseases.

Parkin, an E3 ubiquitin ligase, has been found to be responsible for autosomal recessive juvenile parkinsonism characterized primarily by selective loss of dopaminergic neurons with subsequent defects in movements. However, the molecular mechanisms underlying this neuron loss remain elusive. Here, we characterizedDrosophila parkinloss-of-function mutants, which exhibit shrinkage of dopaminergic neurons with decreased tyrosine hydroxylase level and impaired locomotion. The behavioral defect ofparkinmutant flies was partially restored by administering L-DOPA, and the dopamine level in the brains of parkin mutant flies was highly decreased. Intriguingly, we found that c-Jun N-terminal kinase (JNK) is strongly activated in the dopaminergic neurons ofparkinmutants and that impaired dopaminergic neuron phenotypes are dependent on the activation of the JNK signaling pathway. In consistent with this, our epistatic analysis and mammalian cell studies showed that Parkin inhibits the JNK signaling pathway in an E3 activity-dependent manner. These results suggest that loss of Parkin function up-regulates the JNK signaling pathway, which may contribute to the vulnerability of dopaminergic neurons inDrosophila parkinmutants and perhaps autosomal recessive juvenile parkinsonism patients.

Carotenoids, symmetrical tetraterpenes with a linear C40 hydrocarbon backbone, are natural pigment molecules produced by plants, algae, and fungi. Carotenoids have important functions in the organisms (including animals) that obtain them from food. Due to their characteristic structure, carotenoids have bioactive properties, such as antioxidant, anti‐inflammatory, and autophagy‐modulatory activities. Given the protective function of carotenoids, their levels in the human body have been significantly associated with the treatment and prevention of various diseases, including neurodegenerative diseases. In this paper, we review the latest studies on the effects of carotenoids on neurodegenerative diseases in humans. Furthermore, animal and cellular model studies on the beneficial effects of carotenoids on neurodegeneration are also reviewed. Finally, we discuss the possible mechanisms and limitations of carotenoids in the treatment and prevention of neurological diseases.

Two Drosophila tumor necrosis factor receptor-associated factors (TRAF), DTRAF1 and DTRAF2, are proposed to have similar functions with their mammalian counterparts as a signal mediator of cell surface receptors. However, their in vivo functions and related signaling pathways are not fully understood yet. Here, we show that DTRAF1 is an in vivo regulator of c-Jun N-terminal kinase (JNK) pathway in Drosophila melanogaster. Ectopic expression of DTRAF1 in the developing eye induced apoptosis, thereby causing a rough-eye phenotype. Further genetic interaction analyses revealed that the apoptosis in the eye imaginal disc and the abnormal eye morphogenesis induced by DTRAF1 are dependent on JNK and its upstream kinases, Hep and DTAK1. In support of these results, DTRAF1-null mutant showed a remarkable reduction in JNK activity with an impaired development of imaginal discs and a defective formation of photosensory neuron arrays. In contrast, DTRAF2 was demonstrated as an upstream activator of nuclear factor-κB (NF-κB). Ectopic expression of DTRAF2 induced nuclear translocation of two Drosophila NF-κBs, DIF and Relish, consequently activating the transcription of the antimicrobial peptide genes diptericin, diptericin-like protein, and drosomycin. Consistently, the null mutant of DTRAF2 showed immune deficiencies in which NF-κB nuclear translocation and antimicrobial gene transcription against microbial infection were severely impaired. Collectively, our findings demonstrate that DTRAF1 and DTRAF2 play pivotal roles in Drosophila development and innate immunity by differentially regulating the JNK- and the NF-κB-dependent signaling pathway, respectively.

Phosphoinositide-dependent kinase-1 (PDK-1) is a central mediator of the cell signaling between phosphoinositide 3-kinase (PI3K) and various intracellular serine/threonine kinases including Akt/protein kinase B (PKB), p70 S6 kinases, and protein kinase C. Recent studies with cell transfection experiments have implied that PDK-1 may be involved in various cell functions including cell growth and apoptosis. However, despite its pivotal role in cellular signalings, the in vivo functions of PDK-1 in a multicellular system have rarely been investigated. Here, we have isolated Drosophila PDK-1 ( dPDK-1 ) mutants and characterized the in vivo roles of the kinase. Drosophila deficient in the dPDK-1 gene exhibited lethality and an apoptotic phenotype in the embryonic stage. Conversely, overexpression of dPDK-1 increased cell and organ size in a Drosophila PI3K-dependent manner. dPDK-1 not only could activate Drosophila Akt/PKB ( Dakt1 ), but also substitute the in vivo functions of its mammalian ortholog to activate Akt/PKB. This functional interaction between dPDK-1 and Dakt1 was further confirmed through genetic analyses in Drosophila . On the other hand, cAMP-dependent protein kinase, which has been proposed as a possible target of dPDK-1 , did not interact with dPDK-1 . In conclusion, our findings provide direct evidence that dPDK-1 regulates cell growth and apoptosis during Drosophila development via the PI3K-dependent signaling pathway and demonstrate our Drosophila system to be a powerful tool for elucidating the in vivo functions and targets of PDK-1.