Neuronal fatty acid-binding protein enhances autophagy and suppresses amyloid-β pathology in a Drosophila model of Alzheimer's disease.

Fatty acid-binding proteins (FABPs) are small cytoplasmic proteins involved in intracellular lipid transport and bind free fatty acids, cholesterol, and retinoids. FABP3, the major neuronal FABP in the adult brain, is upregulated in the CSF of patients with Alzheimer's disease (AD). However, the precise role of neuronal FABPs in AD pathogenesis remains unclear.

Histone methyltransferase NSD modulates gene silencing mechanisms on Drosophila chromosome 4.

The nuclear receptor-binding SET domain protein (NSD) gene family encodes histone methyltransferases that mono- and di-methylate lysine 36 on histone H3 (H3K36). Here, we examine the effects of NSD loss-of-function on transcription and heterochromatin formation in Drosophila to elucidate the role of NSD in chromatin structure regulation. Transcriptome analysis showed that NSD deletion activated more genes on chromosome 4, predominantly heterochromatic, than on other chromosomes.

The role of glial and neuronal Eph/ephrin signaling in Drosophila mushroom body development and sleep and circadian behavior.

The Eph receptor, a prototypically large receptor protein tyrosine kinase, interacts with ephrin ligands, forming a bidirectional signaling system that impacts diverse brain functions. Eph receptors and ephrins mediate forward and reverse signaling, affecting neurogenesis, axon guidance, and synaptic signaling. While mammalian studies have emphasized their roles in neurogenesis and synaptic plasticity, the Drosophila counterparts are less studied, especially in glial cells, despite structural similarities.

Neuroprotective effects of linear ubiquitin E3 ligase against aging-induced DNA damage and amyloid β neurotoxicity in the brain of Drosophila melanogaster.

E3 ubiquitin ligase, HOIL1-interacting protein (HOIP), forms the linear ubiquitin chain assembly complex (LUBAC) with HOIL and SHANK-associated RH domain interactor and catalyzes linear ubiquitination, directly linking the N- and C-termini of ubiquitin. Recently, several studies have implicated linear ubiquitination in aging and Alzheimer disease (AD). However, little is currently known about the roles of HOIP in brain aging and AD pathology.

Roles of in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Model.

Zinc is a fundamental trace element essential for numerous biological processes, and zinc homeostasis is regulated by the Zrt-/Irt-like protein (ZIP) and zinc transporter (ZnT) families. ZnT7 is mainly localized in the Golgi apparatus and endoplasmic reticulum (ER) and transports zinc into these organelles. Although previous studies have reported the role of zinc in animal physiology, little is known about the importance of zinc in the Golgi apparatus and ER in animal development and neurodegenerative diseases.

Conformational change of organic cofactor PLP is essential for catalysis in PLP-dependent enzymes.

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are ubiquitous, catalyzing various biochemical reactions of approximately 4% of all classified enzymatic activities. They transform amines and amino acids into important metabolites or signaling molecules and are important drug targets in many diseases. In the crystal structures of PLP-dependent enzymes, organic cofactor PLP showed diverse conformations depending on the catalytic step.

Functional Characterization of CYP6A8 Fatty Acid Hydroxylase.

Genomic analysis indicated that the genome of contains more than 80 cytochrome P450 genes. To date, the enzymatic activity of these P450s has not been extensively studied. Here, the biochemical properties of CYP6A8 were characterized.

Roles of Drosophila fatty acid-binding protein in development and behavior.

Fatty acid-binding proteins (FABPs) are lipid chaperones that mediate the intracellular dynamics of the hydrophobic molecules that they physically bind to. FABPs are implicated in sleep and psychiatric disorders, as well as in various cellular processes, such as cell proliferation and survival. FABP is well conserved in insects, and Drosophila has one FABP ortholog, dFabp, in its genome.

Cullin 1 (CUL1) Promotes Primary Ciliogenesis through the Induction of Ubiquitin-Proteasome-Dependent Dvl2 Degradation.

Primary cilia are nonmotile cellular signal-sensing antenna-like structures composed of microtubule-based structures that distinguish them from motile cilia in structure and function. Primary ciliogenesis is regulated by various cellular signals, such as Wnt, hedgehog (Hh), and platelet-derived growth factor (PDGF). The abnormal regulation of ciliogenesis is closely related to developing various human diseases, including ciliopathies and cancer.

Physical Exercise-Induced Myokines in Neurodegenerative Diseases.

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.

Drosophila NSD deletion induces developmental anomalies similar to those seen in Sotos syndrome 1 patients.

Background: Haploinsufficiency of the human nuclear receptor binding suppressor of variegation 3-9, enhancer of zeste, and trithorax (SET) domain 1 (NSD1) gene causes a developmental disorder called Sotos syndrome 1 (SOTOS1), which is associated with overgrowth and macrocephaly. NSD family proteins encoding histone H3 lysine 36 (H3K36) methyltransferases are conserved in many species, and Drosophila has a single NSD homolog gene, NSD.

Objective: To gain insight into the biological functions of NSD1 deficiency in the developmental anomalies seen in SOTOS1 patients using an NSD-deleted Drosophila mutant.

Wnt5a-induced docking of Plk1 on HEF1 promotes HEF1 translocation and tumorigenesis.

Background: Upregulation of human enhancer filamentation 1 (HEF1/NEDD9/Cas-L) and Polo-like kinase 1 (Plk1) is closely correlated with metastasis of human cancer. However, the mechanism by which the overexpression of HEF1 or Plk1 stimulates cancer metastasis and induces tumorigenesis remains enigmatic. In addition, the accumulation of HEF1 at the focal adhesion (FA) is known to be an essential event in cancer cell migration, but the mechanism of how HEF1 is targeted to the FA remains yet to be unveiled.

Nicotinamide Supplementation Improves Oocyte Quality and Offspring Development by Modulating Mitochondrial Function in an Aged Model.

Aging is associated with a decline in the quality of biological functions. Among the aging processes, reproductive aging is a critical process because of its intergenerational effects. However, the mechanisms underlying reproductive aging remain largely unknown.

Linalool Alleviates A42-Induced Neurodegeneration via Suppressing ROS Production and Inflammation in Fly and Rat Models of Alzheimer's Disease.

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 (A) and identified linalool as a neuroprotective terpene against A 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.

The linear ubiquitin E3 ligase-Relish pathway is involved in the regulation of proteostasis in Drosophila muscle during aging.

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.

Overexpression of H3K36 methyltransferase NSD in glial cells affects brain development in Drosophila.

NSD1 is a histone methyltransferase that methylates the lysine 36 at histone H3. NSD duplication is associated with short stature, microcephaly, intellectual disability, and behavioral defects in humans. Ectopic overexpression of NSD, an NSD1 homolog in Drosophila, was shown to induce developmental abnormalities via apoptosis.

Neuroprotective effects of Suhexiang Wan on the in vitro and in vivo models of Parkinson's disease.

Objective: To examine the role of KSOP1009 (a modified formulation of Suhexiang Wan essential oil) in an animal model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection.

Methods: Cell toxicity, apoptosis, and reactive oxygen species (ROS) levels were analyzed in the human neuroblastoma cell line SH-SY5Y. After that, changes in animal behavior and tyrosine hydroxylase (TH) protein levels in the substantia nigra (SN) of MPTP-injected mice were examined.

Genetic Dissection of Alzheimer's Disease Using Models.

Alzheimer's disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to abnormal accumulation of the amyloid β (Aβ) protein. Despite decades of intensive research, the mechanisms underlying AD remain elusive, and the only available treatment remains symptomatic. Molecular understanding of the pathogenesis and progression of AD is necessary to develop disease-modifying treatment.

Neuroprotective Effects of Limonene (+) against Aβ42-Induced Neurotoxicity in a Drosophila Model of Alzheimer's Disease.

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.

Neurodevelopmental disorders with epigenetic dysregulation and .

Recently, the mechanisms underlying epigenetic dysregulation associated with neurodevelopmental disorders have attracted increasing attention. Although most neurodevelopmental disorders in humans are multifaceted and encompass a wide range of symptoms, a small number of cases linked to specific single gene disruptions have been identified. The genetic system provides excellent models for such diseases.

Low-dose ionizing radiation alleviates Aβ42-induced cell death via regulating AKT and p38 pathways in Alzheimer's disease models.

Ionizing radiation is widely used in medicine and is valuable in both the diagnosis and treatment of many diseases. However, its health effects are ambiguous. Here, we report that low-dose ionizing radiation has beneficial effects in human amyloid-β42 (Aβ42)-expressing Alzheimer's disease (AD) models.

Autophagy Modulators and Neuroinflammation.

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders.

Recent Advances in Studies on the Therapeutic Potential of Dietary Carotenoids in Neurodegenerative Diseases.

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.

Inhibitory effect of α-terpinyl acetate on cytochrome P450 2B6 enzymatic activity.

Human cytochrome P450 2B6 is an important hepatic enzyme for the metabolism of xenobiotics and clinical drugs. Recently, more attention has been paid to P450 2B6 because of the increasing number of drugs it metabolizes. It has been known to interact with terpenes, the major constituents of the essential oils used for various medicinal purposes.