Progress to Clarify How Mutations Lead to CADASIL, a Hereditary Cerebral Small Vessel Disease.

Notch signaling is conserved in , , and mammals. Among the four genes in humans, , , and are known to cause monogenic hereditary disorders. Most -related disorders are congenital and caused by a gain or loss of Notch signaling activity.

Role of in Human Disease Research 3.0.

has become a commonly used animal model for biomedical research in a variety of areas [...

A Novel Drosophila-based Drug Repurposing Platform Identified Fingolimod As a Potential Therapeutic for TDP-43 Proteinopathy.

Pathogenic changes to TAR DNA-binding protein 43 (TDP-43) leading to alteration of its homeostasis are a common feature shared by several progressive neurodegenerative diseases for which there is no effective therapy. Here, we developed Drosophila lines expressing either wild type TDP-43 (WT) or that carrying an Amyotrophic Lateral Sclerosis /Frontotemporal Lobar Degeneration-associating G384C mutation that recapitulate several aspects of the TDP-43 pathology. To identify potential therapeutics for TDP-43-related diseases, we implemented a drug repurposing strategy that involved three consecutive steps.

Association of Mutations in Replicative DNA Polymerase Genes with Human Disease: Possible Application of Models for Studies.

Replicative DNA polymerases, such as DNA polymerase α-primase, δ and ε, are multi-subunit complexes that are responsible for the bulk of nuclear DNA replication during the S phase. Over the last decade, extensive genome-wide association studies and expression profiling studies of the replicative DNA polymerase genes in human patients have revealed a link between the replicative DNA polymerase genes and various human diseases and disorders including cancer, intellectual disability, microcephalic primordial dwarfism and immunodeficiency. These studies suggest the importance of dissecting the mechanisms involved in the functioning of replicative DNA polymerases in understanding and treating a range of human diseases.

Drosophila transcription factor NF-Y suppresses transcription of the lipase 4 gene, a key gene for lipid storage.

The CCAAT motif-binding factor NF-Y consists of three different subunits, NF-YA, NF-YB, and NF-YC. Although it is suggested that NF-Y activity is essential for normal tissue homeostasis, survival, and metabolic function, its precise role in lipid metabolism is not clarified yet. In Drosophila, eye disc specific knockdown of Drosophila NF-YA (dNF-YA) induced aberrant morphology of the compound eye, the rough eye phenotype in adults and mutation of the lipase 4 (lip4) gene suppressed the rough eye phenotype.

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 β cells and has been implicated in β cells' viability and function, however, the role of UCH-L1 in β cells remains unclear. Herein, we examined the functions of UCH-L1 in β cells by utilizing the Drosophila melanogaster model. Our results showed that specific knockdown of dUCH (D.

Role of in Human Disease Research 2.0.

The fruit fly is a highly tractable animal model to study various human diseases [...

Crucial Roles of Ubiquitin Carboxy-Terminal Hydrolase L1 in Motor Neuronal Health by Model.

Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) plays an important role in the ubiquitin-proteasome system and is distributed mostly in the brain. Previous studies have shown that mutated forms or reduction of UCH-L1 are related to neurodegenerative disorders, but the mechanisms of pathogenesis are still not well understood. To study its roles in motor neuronal health, we utilized the model in which , a homolog of human , was specifically knocked down in motor neurons.

Complex hereditary peripheral neuropathies caused by novel variants in mitochondrial-related nuclear genes.

Mitochondrial disorders are a group of clinically and genetically heterogeneous multisystem disorders and peripheral neuropathy is frequently described in the context of mutations in mitochondrial-related nuclear genes. This study aimed to identify the causative mutations in mitochondrial-related nuclear genes in suspected hereditary peripheral neuropathy patients. We enrolled a large Japanese cohort of clinically suspected hereditary peripheral neuropathy patients who were mutation negative in the prescreening of the known Charcot-Marie-Tooth disease-causing genes.

The function of Scox in glial cells is essential for locomotive ability in Drosophila.

Synthesis of cytochrome c oxidase (Scox) is a Drosophila homolog of human SCO2 encoding a metallochaperone that transports copper to cytochrome c, and is an essential protein for the assembly of cytochrome c oxidase in the mitochondrial respiratory chain complex. SCO2 is highly conserved in a wide variety of species across prokaryotes and eukaryotes, and mutations in SCO2 are known to cause mitochondrial diseases such as fatal infantile cardioencephalomyopathy, Leigh syndrome, and Charcot-Marie-Tooth disease, a neurodegenerative disorder. These diseases have a common symptom of locomotive dysfunction.

Polymorphism of Gene in Vietnamese Gastric Cancer Patients: A Multicenter Case-Control Study.

Background: A few studies revealed that the polymorphisms of gene have a role and significance as a susceptible factor contributing to gastric cancer. To better understand the roles of two genotype polymorphisms of rs4072037 and rs2070803 in the development of gastric cancer in Vietnamese population, a multicenter, large-sample, case-control study was conducted to investigate the potential association of these single-nucleotide polymorphisms (SNPs) of gene with gastric cancer risk and to evaluate the combination factors in relation with these SNPs.

Methods: This case-control study included 302 gastric cancer patients and 304 controls at four national medical hospitals between 2016 and 2018.

Identification of Rpd3 as a novel epigenetic regulator of Drosophila FIG 4, a Charcot-Marie-Tooth disease-causing gene.

Mutations in the factor-induced-gene 4 (FIG 4) gene are associated with multiple disorders, including Charcot-Marie-Tooth disease (CMT), epilepsy with polymicrogyria, Yunis-Varón syndrome and amyotrophic lateral sclerosis. The wide spectrum of disorders associated with FIG 4 may be related to the dysregulated epigenetics. Using Gene Expression Omnibus, we found that HDAC1 binds to the FIG 4 gene locus in the genome of human CD4+ T cells.

Drosophila models to study causative genes for human rare intractable neurological diseases.

Drosophila is emerging as a convenient model for investigating human diseases. Functional homologues of almost 75% of human disease-related genes are found in Drosophila. Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes defects in motoneurons.

Gene expression of PLAT and ATS3 proteins increases plant resistance to insects.

Genes of the PLAT protein family, including PLAT and ATS3 subfamilies of higher plants and homologs of liverwort, are involved in plant defense against insects. Laticifer cells in plants contain large amounts of anti-microbe or anti-insect proteins and are involved in plant defense against biotic stresses. We previously found that PLAT proteins accumulate in laticifers of fig tree (Ficus carica) at comparable levels to those of chitinases, and the transcript level of ATS3, another PLAT domain-containing protein, is highest in the transcriptome of laticifers of Euphorbia tirucalli.

Epigenetic Regulation of ALS and CMT: A Lesson from Models.

Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disorder and is sometimes associated with frontotemporal dementia. Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited peripheral neuropathies causing the slow progression of sensory and distal muscle defects. Of note, the severity and progression of CMT symptoms markedly vary.

Correction: Ueoka, I., et al. Autism Spectrum Disorder-Related Syndromes: Modeling with and Rodents. 2019, , 4071.

The author wishes to make the following correction to this paper [...

A novel Drosophila model for neurodevelopmental disorders associated with Shwachman-Diamond syndrome.

Genetic defects in ribosome biogenesis result in a group of diseases called ribosomopathies. Patients with ribosomopathies manifest multiorgan phenotypes, including neurological impairments. A well-characterized ribosomopathy, Shwachman-Diamond syndrome (SDS), is mainly associated with loss-of-function mutations in the causal gene SBDS.

Investigating Developmental and Epileptic Encephalopathy Using .

Developmental and epileptic encephalopathies (DEEs) are the spectrum of severe epilepsies characterized by early-onset, refractory seizures occurring in the context of developmental regression or plateauing. Early infantile epileptic encephalopathy (EIEE) is one of the earliest forms of DEE, manifesting as frequent epileptic spasms and characteristic electroencephalogram findings in early infancy. In recent years, next-generation sequencing approaches have identified a number of monogenic determinants underlying DEE.

Honeybee products and edible insect powders improve locomotive and learning abilities of Ubiquilin-knockdown Drosophila.

Background: Mutations in the human Ubiquilin 2 gene are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD), the fatal neurodegenerative disease that progressively affected neuronal cells in both brain and spinal cord. There is currently no effective therapy for these diseases. Over the last decade, researchers have focused on the potential use of natural products especially in neurodegenerative studies.

Novel Drosophila model for parkinsonism by targeting phosphoglycerate kinase.

Patients with Parkinson's disease (PD) show a common progressive neurodegenerative movement disorder characterized by rigidity, tremors, postural instability, and bradykinesia due to the loss of dopaminergic neurons in the substantia nigra, and is often accompanied by several non-motor symptoms, called parkinsonism. Several lines of recent evidence support the hypothesis that mutations in the gene encoding phosphoglycerate kinase (PGK) play an important role in the PD mechanism. PGK is a key enzyme in the glycolytic pathway that catalyzes the reaction from 1,3-diphosphoglycerate to 3-phosphoglycerate.

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.

(L.) Wettst. Extract Improves Memory Performance via Promotion of Neurogenesis in the Hippocampal Dentate Gyrus of Adolescent Mice.

L. Wettst. (BM) is a botanical component of Ayurvedic medicines and of dietary supplements used worldwide for cognitive health and function.