ABSTRACT
Linear ubiquitination is an atypic ubiquitination process that directly connects the N- and C-termini of ubiquitin and is catalyzed by HOIL-1-interacting protein (HOIP). It is involved in the immune response or apoptosis by activating the nuclear factor-κB pathway and is associated with polyglucosan body myopathy 1, an autosomal recessive disorder with progressive muscle weakness and cardiomyopathy. However, little is currently known regarding the function of linear ubiquitination in muscles. Here, we investigated the role of linear ubiquitin E3 ligase (LUBEL), a DrosophilaHOIP ortholog, in the development and aging of muscles. The muscles of the flies with down-regulation of LUBEL or its downstream factors, kenny and Relish, developed normally, and there were no obvious abnormalities in function in young flies. However, the locomotor activity of the LUBEL RNAi flies was reduced compared to age-matched control, while LUBEL RNAi did not affect the increased mitochondrial fusion or myofiber disorganization during aging. Interestingly, the accumulation of polyubiquitinated protein aggregation during aging decreased in muscles by silencing LUBEL, kenny, or Relish. Meanwhile, the levels of autophagy and global translation, which are implicated in the maintenance of proteostasis, did not change due to LUBEL down-regulation. In conclusion, we propose a new role of linear ubiquitination in proteostasis in the muscle aging.
Subject(s)
Aging/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Muscles/metabolism , Proteostasis , Transcription Factors/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Autophagy , Down-Regulation , Drosophila Proteins/genetics , Drosophila melanogaster/enzymology , Gene Silencing , I-kappa B Kinase/deficiency , I-kappa B Kinase/metabolism , Locomotion , Male , Muscle Strength , Muscles/enzymology , NF-kappa B/metabolism , Polyubiquitin/metabolism , Protein Aggregates , Protein Biosynthesis , Transcription Factors/genetics , Ubiquitin-Protein Ligases/genetics , UbiquitinationABSTRACT
Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), are disorders characterized by progressive degeneration of the nervous system. Currently, there is no disease-modifying treatments for most NDs. Meanwhile, numerous studies conducted on human and animal models over the past decades have showed that exercises had beneficial effects on NDs. Inter-tissue communication by myokine, a peptide produced and secreted by skeletal muscles during exercise, is thought to be an important underlying mechanism for the advantages. Here, we reviewed studies about the effects of myokines regulated by exercise on NDs and their mechanisms. Myokines could exert beneficial effects on NDs through a variety of regulatory mechanisms, including cell survival, neurogenesis, neuroinflammation, proteostasis, oxidative stress, and protein modification. Studies on exercise-induced myokines are expected to provide a novel strategy for treating NDs, for which there are no adequate treatments nowadays. To date, only a few myokines have been investigated for their effects on NDs and studies on mechanisms involved in them are in their infancy. Therefore, future studies are needed to discover more myokines and test their effects on NDs.
Subject(s)
Cytokines/metabolism , Exercise/physiology , Muscle, Skeletal/metabolism , Neurodegenerative Diseases/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/physiopathology , Animals , Humans , Huntington Disease/metabolism , Huntington Disease/physiopathology , Neurodegenerative Diseases/physiopathology , Parkinson Disease/metabolism , Parkinson Disease/physiopathologyABSTRACT
Forest bathing is suggested to have beneficial effects on various aspects of human health. Terpenes, isoprene based-phytochemicals emitted from trees, are largely responsible for these beneficial effects of forest bathing. Although the therapeutic effects of terpenes on various diseases have been revealed, their effects on neuronal health have not yet been studied in detail. Here, we screened 16 terpenes that are the main components of Korean forests using Drosophila Alzheimer's disease (AD) models to identify which terpenes have neuroprotective effects. Six out of the 16 terpenes, ρ-cymene, limonene (+), limonene (-), linalool, α-pinene (+), and ß-pinene (-), partially suppressed the beta amyloid 42 (Aß42)-induced rough eye phenotype when fed to Aß42-expressing flies. Among them, limonene (+) restored the decreased survival of flies expressing Aß42 in neurons during development. Limonene (+) treatment did not affect Aß42 accumulation and aggregation, but did cause to decrease cell death, reactive oxygen species levels, extracellular signal-regulated kinase phosphorylation, and inflammation in the brains or the eye imaginal discs of Aß42-expressing flies. This neuroprotective effect of limonene (+) was not associated with autophagic activity. Our results suggest that limonene (+) has a neuroprotective function against the neurotoxicity of Aß42 and, thus, is a possible therapeutic reagent for AD.
Subject(s)
Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Limonene/pharmacology , Neuroprotective Agents/pharmacology , Terpenes/pharmacology , Amyloid beta-Peptides/toxicity , Animals , Animals, Genetically Modified , Autophagy/drug effects , Brain/metabolism , Disease Models, Animal , Drosophila melanogaster , MAP Kinase Signaling System/drug effects , Neuroglia/drug effects , Peptide Fragments/toxicity , Phosphorylation/drug effects , Reactive Oxygen Species/metabolism , SurvivalABSTRACT
In this study, the physical and electrical characteristics of an AlN/4H-SiC Schottky barrier diode-based temperature sensor annealed in various gas atmospheres were investigated. An aluminum nitride (AlN) thin film was deposited on a 4H-SiC substrate via radio-frequency sputtering followed by annealing in N2 or O2 gas. The chemical composition of the film was determined by X-ray photoelectron spectroscopy (XPS) before and after annealing, and its electrical properties were evaluated by plotting a current-voltage (I-V) curve. The voltage-temperature (V-T) characteristics of the sensor were extracted from the current-voltage-temperature (I-V-T) plots constructed in the temperature range between 475 and 300 K in steps of 25 K. Sensitivities of 9.77, 9.37, and 2.16 mV/K were obtained for the as-grown, N2-annealed, and O2-annealed samples, respectively.
ABSTRACT
In this study, static induction transistors (SITs) with beta gallium oxide (ß-Ga2O3) channels are grown on a p-epi silicon carbide (SiC) layer via radio frequency sputtering. The Ga2O3 films are subjected to UV/ozone treatment, which results in reduced oxygen vacancies in the X-ray photoelectron spectroscopy data, lower surface roughness (3.51 nm) and resistivity (319 Ω·cm), and higher mobility (4.01 cm2V-1s-1). The gate leakage current is as low as 1.0 × 10-11 A at VGS = 10 V by the depletion layer formed between n-Ga2O3 and p-epi SiC at the gate region with a PN heterojunction. The UV/O3-treated SITs exhibit higher (approximately 1.64 × 102 times) drain current (VDS = 12 V) and on/off ratio (4.32 × 105) than non-treated control devices.
ABSTRACT
Terpenes are vital metabolites found in various plants and animals and known to be beneficial in the treatment of various diseases. Previously, our group identified terpenes that increased the survival of Alzheimer's disease (AD) model flies expressing human amyloid ß (Aß) and identified linalool as a neuroprotective terpene against Aß toxicity. Linalool is a monoterpene that is commonly present as a constituent in essential oils from aromatic plants and is known to have anti-inflammatory, anticancer, antihyperlipidemia, antibacterial, and neuroprotective properties. Although several studies have shown the beneficial effect of linalool in AD animal models, the mechanisms underlying the beneficial effect of linalool on AD are yet to be elucidated. In the present study, we showed that linalool intake increased the survival of the AD model flies during development in a dose-dependent manner, while the survival of wild-type flies was not affected even at high linalool concentrations. Linalool also decreases Aß-induced apoptosis in eye discs as well as the larval brain. Moreover, linalool intake was found to reduce neurodegeneration in the brain of adult AD model flies. However, linalool did not affect the total amount of Aß42 protein or Aß42 aggregation. Rather, linalool decreased Aß-induced ROS levels, oxidative stress, and inflammatory response in the brains of AD model flies. Furthermore, linalool attenuated the induction of oxidative stress and gliosis by Aß 1-42 treatment in the rat hippocampus. Taken together, our data suggest that linalool exerts its beneficial effects on AD by reducing Aß42-induced oxidative stress and inflammatory reactions.
Subject(s)
Acyclic Monoterpenes/pharmacology , Alzheimer Disease , Amyloid beta-Peptides/metabolism , Peptide Fragments/metabolism , Reactive Oxygen Species/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/genetics , Animals , Disease Models, Animal , Drosophila melanogaster , Peptide Fragments/genetics , Rats , Rats, Sprague-DawleyABSTRACT
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.