Elevated Neuronal Excitability Due to Modulation of the Voltage-Gated Sodium Channel Nav1.6 by Aβ1-42.

Aberrant increases in neuronal network excitability may contribute to the cognitive deficits in Alzheimer's disease (AD). However, the mechanisms underlying hyperexcitability are not fully understood. Such overexcitation of neuronal networks has been detected in the brains of APP/PS1 mice.

Calmodulin activity regulates group I metabotropic glutamate receptor-mediated signal transduction and synaptic depression.

Group I metabotropic glutamate receptors (mGluR), including mGluR1 and mGluR 5 (mGluR1/5), are coupled to Gq and modulate activity-dependent synaptic plasticity. Direct activation of mGluR1/5 causes protein translation-dependent long-term depression (LTD). Although it has been established that intracellular Ca(2+) and the Gq-regulated signaling molecules are required for mGluR1/5 LTD, whether and how Ca(2+) regulates Gq signaling and upregulation of protein expression remain unknown.

Ginkgetin Ameliorates Neuropathological Changes in APP/PS1 Transgenical Mice Model.

The extracellular accumulation of amyloid beta protein (Aβ), reactive gliosis and cerebral amyloid angiopathy (CAA) play critical roles in the pathogenesis of Alzheimer's disease (AD). Ginkgetin, a biflavone isolated from Ginkgo biloba leaves, was previously reported to exhibit strong neuroprotection against cytotoxic insults induced by oxidative stress and amyloid beta, but it remains unclear whether ginkgetin has therapeutic effect on Alzheimer's disease (AD) in vivo. In the present study, we investigated 9 months treatment effects of ginkgetin diet in APP/PS1 mice.

All Ca(2+)-binding loops of light-sensitive ctenophore photoprotein berovin bind magnesium ions: The spatial structure of Mg(2+)-loaded apo-berovin.

Light-sensitive photoprotein berovin accounts for a bright bioluminescence of ctenophore Beroe abyssicola. Berovin is functionally identical to the well-studied Ca(2+)-regulated photoproteins of jellyfish, however in contrast to those it is extremely sensitive to the visible light. Berovin contains three EF-hand Ca(2+)-binding sites and consequently belongs to a large family of the EF-hand Ca(2+)-binding proteins.

Scutellarin Alleviates Behavioral Deficits in a Mouse Model of Multiple Sclerosis, Possibly Through Protecting Neural Stem Cells.

Scutellarin, a flavonoid extracted from an herbal medication (Erigeron breviscapus Hand-Mazz), has been shown to protect neurons against damage and to promote neurogenesis, and thus has therapeutic potential in the treatment of a variety of neurodegenerative diseases. Since neural stem cells (NSCs) could differentiate into myelin-producing oligodendrocytes, we speculate that scutellarin could also be used to treat multiple sclerosis (MS). In the current study, we examined potential effects of scutellarin using a mouse model of MS.

CXCL1 Triggers Caspase-3 Dependent Tau Cleavage in Long-Term Neuronal Cultures and in the Hippocampus of Aged Mice: Implications in Alzheimer's Disease.

Truncation of tau protein is considered an early event in Alzheimer's disease (AD) and is believed to play a major pathogenic role in sporadic AD. However, causative factors that trigger tau truncation in AD remain poorly understood. In the present study, we demonstrate that CXCL1 (C-X-C motif ligand 1), a specific ligand for the chemokine receptor CXCR2, induced cleavage of tau at ASP421 in a caspase-3-dependent manner in long-term but not short-term cultured neurons.

New insights into the structural basis of DNA recognition by HINa and HINb domains of IFI16.

Interferon gamma-inducible protein 16 (IFI16) senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear (HIN) domains, HINa and HINb, through the cooperative assembly of IFI16 filaments on double-stranded DNA (dsDNA). The role of HINa in sensing DNA is not clearly understood. Here, we describe the crystal structure of the HINa domain in complex with DNA at 2.

Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues.

There are two forms of brain-derived neurotrophic factor (BDNF), precursor of BDNF (proBDNF) and mature BDNF, which each exert opposing effects through two different transmembrane receptor signaling systems, consisting of p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB). Previous studies have demonstrated that proBDNF promotes cell death and inhibits the growth and migration of C6 glioma cells through p75NTR , while mature BDNF has opposite effects on C6 glioma cells. It is hypothesized that mature BDNF is essential in the development of malignancy in gliomas.

p75NTR ectodomain is a physiological neuroprotective molecule against amyloid-beta toxicity in the brain of Alzheimer's disease.

In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known.

Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression.

Amyloid precursor protein enhances Nav1.6 sodium channel cell surface expression.

Amyloid precursor protein (APP) is commonly associated with Alzheimer disease, but its physiological function remains unknown. Nav1.6 is a key determinant of neuronal excitability in vivo.

Mice deficient for wild-type p53-induced phosphatase 1 display elevated anxiety- and depression-like behaviors.

Mood disorders are a severe health burden but molecular mechanisms underlying mood dysfunction remain poorly understood. Here, we show that wild-type p53-induced phosphatase 1 (Wip1) negatively responds to the stress-induced negative mood-related behaviors. Specifically, we show that Wip1 protein but not its mRNA level was downregulated in the hippocampus but not in the neocortex after 4 weeks of chronic unpredictable mild stress (CUMS) in mice.

Inhibition of wild-type p53-induced phosphatase 1 promotes liver regeneration in mice by direct activation of mammalian target of rapamycin.

Unlabelled: The liver possesses extraordinary regenerative capacity in response to injury. However, liver regeneration (LR) is often impaired in disease conditions. Wild-type p53-induced phosphatase 1 (Wip1) is known as a tumor promoter and enhances cell proliferation, mainly by deactivating antioncogenes.

APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation.

Amyloid precursor protein (APP) is best known for its involvement in the pathogenesis of Alzheimer's disease. We have previously demonstrated that APP intracellular domain (AICD) regulates neurogenesis; however, the mechanisms underlying AICD-mediated regulation of neuronal differentiation are not yet fully characterized. Using genome-wide chromatin immunoprecipitation approaches, we found that AICD is specifically recruited to the regulatory regions of several microRNA genes, and acts as a transcriptional regulator for miR-663, miR-3648 and miR-3687 in human neural stem cells.

Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated with Synaptic Plasticity and Expression of COX5A and FGF-2.

The role of sodium channel voltage-gated beta 2 (SCN2B) in brain aging is largely unknown. The present study was therefore designed to determine the role of SCN2B in brain aging by using the senescence-accelerated mice prone 8 (SAMP8), a brain senescence-accelerated animal model, together with the SCN2B transgenic mice. The results showed that SAMP8 exhibited impaired learning and memory functions, assessed by the Morris water maze test, as early as 8 months of age.

The Ca(2+) channel inhibitor 2-APB reverses β-amyloid-induced LTP deficit in hippocampus by blocking BAX and caspase-3 hyperactivation.

Background And Purpose: At the early stage of Alzheimer's disease (AD), the accumulation of β-amyloid (Aβ) oligomers disturbs intracellular Ca(2+) homeostasis and disrupts synaptic plasticity of brain neurons. Prevention of Aβ-induced synaptic failure remains an unsolved problem for the treatment of AD. Here, the effects of 2-aminoethoxydiphenyl borate (2-APB), a non-specific, but moderately potent Ca(2+) channel inhibitor, on Aβ-induced deficit of synaptic long-term potentiation (LTP) and the underlying molecular mechanisms were explored.

General public perceptions and attitudes toward Alzheimer's disease from five cities in China.

Alzheimer's disease (AD) is the most common type of dementia affecting the aged population worldwide, yet its social perceptions have been less studied. To investigate the perceptions and attitudes toward AD in the Chinese population, a cross-sectional face-to-face survey of 2,000 randomly selected adults was conducted in five representative cities of China. This survey focused on the fear of AD, and the relationship between this variable and each studied factor was analyzed using univariate analysis and multivariate regression analysis.

Effects of (-)Epicatechin on the Pathology of APP/PS1 Transgenic Mice.

Background: Alzheimer's disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The clearance of Aβ from the brain and anti-inflammation are potential important strategies to prevent and treat disease. In a previous study, we demonstrated the grape seed extract (GSE) could reduce brain Aβ burden and microglia activation, but which polyphenol plays a major role in these events is not known.

Deletion of TRIM32 protects mice from anxiety- and depression-like behaviors under mild stress.

Chronic stress causes a variety of psychiatric disorders such as anxiety and depression, but its mechanism is not well understood. Tripartite motif-containing protein 32 (TRIM32) was strongly associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety and obsessive compulsive disorder based on a study of copy number variation, and deletion of TRIM32 increased neural proliferation and reduced apoptosis. Here, we propose that TRIM32 is involved in chronic stress-induced affective behaviors.

Species-dependent neuropathology in transgenic SOD1 pigs.

Mutations in the human copper/zinc superoxide dismutase 1 (hSOD1) gene cause familial amyotrophic lateral sclerosis (ALS). It remains unknown whether large animal models of ALS mimic more pathological events seen in ALS patients via novel mechanisms. Here, we report the generation of transgenic pigs expressing mutant G93A hSOD1 and showing hind limb motor defects, which are germline transmissible, and motor neuron degeneration in dose- and age-dependent manners.

MicroRNA-195 inhibits non-small cell lung cancer cell proliferation, migration and invasion by targeting MYB.

MicroRNA-195 (miR-195) has been implicated in several other cancers; however, its role in non-small cell lung cancer (NSCLC) remains unclear. In this study, we demonstrated that miR-195 was significantly down-regulated in NSCLC samples and cell lines compared with corresponding normal counterparts. In vitro and in vivo functional assays demonstrated that modulation of miR-195 expression affected NSCLC cell proliferation, migration and invasion.

Pulmonary arterial hypertension in HIV infection: a concise review.

Pulmonary arterial hypertension (PAH) is an infrequent but nevertheless serious life threatening severe complication of human immunodeficiency virus (HIV) infection. In today's era of antiretroviral therapy (ART), the mortality of HIV patients has greatly reduced due to improved immune function and fewer opportunistic infections. However, these patients have an increased incidence of PAH.

Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis.

There is currently great interest in the use of mesenchymal stem cells as a therapy for multiple sclerosis with potential to both ameliorate inflammatory processes as well as improve regeneration and repair. Although most clinical studies have used autologous bone marrow-derived mesenchymal stem cells, other sources such as allogeneic umbilical cord-derived cells may provide a more accessible and practical supply of cells for transplantation. In this case report we present the treatment of aggressive multiple sclerosis with multiple allogenic human umbilical cord-derived mesenchymal stem cell and autologous bone marrow-derived mesenchymal stem cells over a 4 y period.