Tdrd3-null mice show post-transcriptional and behavioral impairments associated with neurogenesis and synaptic plasticity.

The Topoisomerase 3B (Top3b) - Tudor domain containing 3 (Tdrd3) protein complex is the only dual-activity topoisomerase complex that can alter both DNA and RNA topology in animals. TOP3B mutations in humans are associated with schizophrenia, autism and cognitive disorders; and Top3b-null mice exhibit several phenotypes observed in animal models of psychiatric and cognitive disorders, including impaired cognitive and emotional behaviors, aberrant neurogenesis and synaptic plasticity, and transcriptional defects. Similarly, human TDRD3 genomic variants have been associated with schizophrenia, verbal short-term memory and educational attainment.

Interaction between GPR110 (ADGRF1) and tight junction protein occludin implicated in blood-brain barrier permeability.

Activation of adhesion receptor GPR110 by the endogenous ligand synaptamide promotes neurogenesis, neurite growth, and synaptogenesis in developing brains through cAMP signal transduction. However, interacting partners of GPR110 and their involvement in cellular function remain unclear. Here, we demonstrate using chemical crosslinking, affinity purification, and quantitative mass spectrometry that GPR110 interacts with the tight junction adhesion protein occludin.

Tdrd3-null mice show post-transcriptional and behavioral impairments associated with neurogenesis and synaptic plasticity.

The Topoisomerase 3B (Top3b) - Tudor domain containing 3 (Tdrd3) protein complex is the only dual-activity topoisomerase complex in animals that can alter the topology of both DNA and RNA. mutations in humans are associated with schizophrenia, autism and cognitive disorders; and -null mice exhibit several phenotypes observed in animal models of psychiatric and cognitive disorders, including impairments in cognitive and emotional behaviors, aberrant neurogenesis and synaptic plasticity, and transcriptional defects. Similarly, human genomic variants have been associated with schizophrenia, verbal shorten-memory and learning, and educational attainment.

Local Protein Translation and RNA Processing of Synaptic Proteins in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD.

Topoisomerase 3β knockout mice show transcriptional and behavioural impairments associated with neurogenesis and synaptic plasticity.

Topoisomerase 3β (Top3β) is the only dual-activity topoisomerase in animals that can change topology for both DNA and RNA, and facilitate transcription on DNA and translation on mRNAs. Top3β mutations have been linked to schizophrenia, autism, epilepsy, and cognitive impairment. Here we show that Top3β knockout mice exhibit behavioural phenotypes related to psychiatric disorders and cognitive impairment.

Properties of Individual Hippocampal Synapses Influencing NMDA-Receptor Activation by Spontaneous Neurotransmission.

NMDA receptor (NMDAR) activation is critical for maintenance and modification of synapse strength. Specifically, NMDAR activation by spontaneous glutamate release has been shown to mediate some forms of synaptic plasticity as well as synaptic development. Interestingly, there is evidence that within individual synapses each release mode may be segregated such that postsynaptically there are distinct pools of responsive receptors.

Topoisomerase 3β interacts with RNAi machinery to promote heterochromatin formation and transcriptional silencing in Drosophila.

Topoisomerases solve topological problems during DNA metabolism, but whether they participate in RNA metabolism remains unclear. Top3β represents a family of topoisomerases carrying activities for both DNA and RNA. Here we show that in Drosophila, Top3β interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) containing AGO2, p68 RNA helicase, and FMRP.

Involvement of 14-3-3 in tubulin instability and impaired axon development is mediated by Tau.

14-3-3 proteins act as adapters that exert their function by interacting with their various protein partners. 14-3-3 proteins have been implicated in a variety of human diseases including neurodegenerative diseases. 14-3-3 proteins have recently been reported to be abundant in the neurofibrillary tangles (NFTs) observed inside the neurons of brains affected by Alzheimer's disease (AD).

In vivo imaging of human adipose-derived stem cells in Alzheimer's disease animal model.

Stem cell therapy is a promising tool for the treatment of diverse conditions, including neurodegenerative diseases such as Alzheimer's disease (AD). To understand transplanted stem cell biology, in vivo imaging is necessary. Nanomaterial has great potential for in vivo imaging and several noninvasive methods are used, such as magnetic resonance imaging, positron emission tomography, fluorescence imaging (FI) and near-infrared FI.

The therapeutic effects of human adipose-derived stem cells in Alzheimer's disease mouse models.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease, still lacking proper clinical treatment. Therefore, many researchers have focused on the possibility of therapeutic use of stem cells for AD. Adipose-derived stem cells (ASCs), mesenchymal stem cells (MSCs) isolated from adipose tissue, are well known for their pluripotency and their ability to differentiate into multiple tissue types and have immune modulatory properties similar to those of MSCs from other origins.

Plasminogen activator inhibitor-1 promotes synaptogenesis and protects against aβ(1-42)-induced neurotoxicity in primary cultured hippocampal neurons.

Plasminogen activator inhibitor-1 (PAI-1) is a soluble factor that is released from astrocytes, the most abundant type of glial cell in the brain. PAI-1 was initially identified as inhibiting two types of plasminogen activators, that is, tissue-type plasminogen and urokinase activators that are known to lead to the proteolytic degradation of the extracellular matrix. Recently, PAI-1 was reported to mediate the neuroprotective activity of transforming growth factor-β1 against N-methyl-D-aspartate receptor-mediated excitotoxicity and to be involved in angiogenesis following ischemic stroke, independently of the effects via the inhibition of tissue-type plasminogen and urokinase-type plasminogen activators.

Therapeutic potentials of neural stem cells treated with fluoxetine in Alzheimer's disease.

Recent studies have proposed that chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. However, the effect of antidepressants on fetal neural stem cells (NSCs) has not been well defined. Our study shows the dose-dependent effects of fluoxetine on the proliferation and neural differentiation of NSCs.

Amyloid precursor protein binding protein-1 knockdown reduces neuronal differentiation in fetal neural stem cells.

Amyloid precursor protein binding protein-1 (APP-BP1) was first identified as an interacting protein of APP. In this study, we explored whether APP-BP1 plays a role in neuronal differentiation of fetal neural stem cells. APP-BP1 knockdown by small interfering RNA treatment was found to downregulate neuronal differentiation and to upregulate APP intracellular domain production from APP in fetal neural stem cells.

Focal transient ischemia increases APP-BP1 expression in neural progenitor cells.

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of APP. In this study, we explored whether APP-BP1 expression is affected by focal transient cerebral ischemia induced by middle cerebral artery occlusion in Wistar rats. APP-BP1 expression was increased in the dentate gyrus of the hippocampus and in the subventricular zone of rats exposed to focal transient cerebral ischemia.

Amyloid precursor protein binding protein-1 modulates cell cycle progression in fetal neural stem cells.

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of the amyloid precursor protein (APP) and serves as the bipartite activation enzyme for the ubiquitin-like protein, NEDD8. In the present study, we explored the physiological role of APP-BP1 in the cell cycle progression of fetal neural stem cells. Our results show that cell cycle progression of the cells is arrested at the G1 phase by depletion of APP-BP1, which results in a marked decrease in the proliferation of the cells.

Amyloid Precursor Protein Binding Protein-1 Is Up-regulated in Brains of Tg2576 Mice.

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP.

Swedish amyloid precursor protein mutation increases cell cycle-related proteins in vitro and in vivo.

Reactivation of the cell cycle, including DNA replication, might play a major role in Alzheimer's disease. In this study, we report that the expressions of Swedish double mutation of amyloid precursor protein (Swe-APP) or of the APP intracellular domain (AICD) into nerve growth factor (NGF)-differentiated PC12 cells or rat primary cortical neurons increased mRNA and protein levels of cyclin D1 and cyclin B1. Treatment with lithium chloride (a glycogen synthase kinase-3beta inhibitor) down-regulated cyclin B1 induced by Swe-APP expression but up-regulated cyclin D1 expression induced by Swe-APP, suggesting that glycogen synthase kinase-3beta activity is involved in these expression changes of cyclins D1 and B1.

Swedish amyloid precursor protein mutation increases phosphorylation of eIF2alpha in vitro and in vivo.

Swedish double mutation (KM670/671NL) of amyloid precursor protein (Swe-APP), a prevailing cause of familial Alzheimer's disease (FAD), is known to increase in Abeta production both in vitro and in vivo, but its underlying molecular basis leading to Alzheimer's disease (AD) pathogenesis remains to be elucidated, especially for the early phase of disease. We have confirmed initially that the expression of Swe-APP mutant transgene reduced cell viability via ROS production but this effect was eliminated by an anti-oxidative agent, vitamin E. We also found that eukaryotic translation initiation factor-2alpha (eIF2alpha), which facilitates binding of initiator tRNA to ribosomes to set on protein synthesis, was phosphorylated in cultured cells expressing Swe-APP.

Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer's disease models.

Nonsteroidal anti-inflammatory drugs (NSAIDs) exert anti-inflammatory, analgesic, and antipyretic activities and suppress prostaglandin synthesis by inhibiting cyclooxygenase, an enzyme that catalyzes the formation of prostaglandin precursors from arachidonic acid. Epidemiological observations indicate that the long-term treatment of patients suffering from rheumatoid arthritis with NSAIDs results in reduced risk and delayed onset of Alzheimer's disease. In this study, we investigated the therapeutic potential for Alzheimer's disease of mefenamic acid, a commonly used NSAID that is a cyclooxygenase-1 and 2 inhibitor with only moderate anti-inflammatory properties.