Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia

Background  

The regulation of protein phosphorylation requires a balance in the activity of protein kinases and protein phosphatases. Our previous data indicates that Src can increase ERK activity through Raf kinase in response to ischemic stimuli. This study examined the molecular mechanisms by which Src activates ERK cascade through protein phosphatases following cerebral ischemia.     

Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice

Background  

The presynaptic protein α-synuclein is involved in a range of neurodegenerative diseases. Here we analyze potential compensatory mechanisms in α-synuclein null mutant mice. Furthermore, the findings reveal problems that may be associated with inbred mouse strains.     

Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants

Background  

Ca²⁺-dependent activator protein 2 (CAPS2/CADPS2) is a secretory vesicle-associated protein involved in the release of neurotrophin. We recently reported that an aberrant, alternatively spliced CAPS2 mRNA that lacks exon 3 (CAPS2Δexon3) is detected in some patients with autism. Splicing variations in mouse CAPS2 and their expression and functions remain unclear.     

A new way to rapidly create functional, fluorescent fusion proteins: random insertion of GFP with an in vitro transposition reaction

Background  

The jellyfish green fluorescent protein (GFP) can be inserted into the middle of another protein to produce a functional, fluorescent fusion protein. Finding permissive sites for insertion, however, can be difficult. Here we describe a transposon-based approach for rapidly creating libraries of GFP fusion proteins.     

Non-invasive quantification of brain tumor-induced astrogliosis

Background  

CNS injury including stroke, infection, and tumor growth lead to astrogliosis, a process that involves upregulation of glial fibrillary acidic protein (GFAP) in astrocytes. However, the kinetics of astrogliosis that is related to these insults (i.e. tumor) is largely unknown.     

Identification of alternatively spliced Dab1 and Fyn isoforms in pig

Background  

Disabled-1 (Dab1) is an adaptor protein that is essential for the intracellular transduction of Reelin signaling, which regulates the migration and differentiation of postmitotic neurons during brain development in vertebrates. Dab1 function depends on its tyrosine phosphorylation by Src family kinases, especially Fyn.     

Amyloid-like aggregates of neuronal tau induced by formaldehyde promote apoptosis of neuronal cells

Background  

The microtubule associated protein tau is the principle component of neurofibrillar tangles, which are a characteristic marker in the pathology of Alzheimer's disease; similar lesions are also observed after chronic alcohol abuse. Formaldehyde is a common environmental contaminant and also a metabolite of methanol. Although many studies have been done on methanol and formaldehyde intoxication, none of these address the contribution of protein misfolding to the pathological mechanism, in particular the effect of formaldehyde on protein conformation and polymerization.     

Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease

Background  

Huntington's Disease (HD) is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt) is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions.     

Male pheromone protein components activate female vomeronasal neurons in the salamander Plethodon shermani

Background  

The mental gland pheromone of male Plethodon salamanders contains two main protein components: a 22 kDa protein named Plethodon Receptivity Factor (PRF) and a 7 kDa protein named Plethodon Modulating Factor (PMF), respectively. Each protein component individually has opposing effects on female courtship behavior, with PRF shortening and PMF lengthening courtship. In this study, we test the hypothesis that PRF or PMF individually activate vomeronasal neurons. The agmatine-uptake technique was used to visualize chemosensory neurons that were activated by each protein component individually.     

Mitochondrial BNIP3 upregulation precedes endonuclease G translocation in hippocampal neuronal death following oxygen-glucose deprivation

Background  

Caspase-independent apoptotic pathways are suggested as a mechanism for the delayed neuronal death following ischemic insult. However, the underlying signalling mechanisms are largely unknown. Recent studies imply the involvement of several mitochondrial proteins, including endonuclease G (EndoG) and Bcl-2/adenovirus E1B 19 kDa-interacting protein (BNIP3), in the pathway of non-neuronal cells.     

Characterization of the beta amyloid precursor protein-like gene in the central nervous system of the crab <Emphasis Type="Italic">Chasmagnathus</Emphasis>. Expression during memory consolidation

Background  

Human β-amyloid, the main component in the neuritic plaques found in patients with Alzheimer's disease, is generated by cleavage of the β-amyloid precursor protein. Beyond the role in pathology, members of this protein family are synaptic proteins and have been associated with synaptogenesis, neuronal plasticity and memory, both in vertebrates and in invertebrates. Consolidation is necessary to convert a short-term labile memory to a long-term and stable form. During consolidation, gene expression and de novo protein synthesis are regulated in order to produce key proteins for the maintenance of plastic changes produced during the acquisition of new information.     

Anti-PrP<Superscript>C</Superscript> monoclonal antibody infusion as a novel treatment for cognitive deficits in an alzheimer's disease model mouse

Background  

Alzheimer's Disease (AD) is the most common of the conformational neurodegenerative disorders characterized by the conversion of a normal biological protein into a β-sheet-rich pathological isoform. In AD the normal soluble Aβ (sAβ) forms oligomers and fibrils which assemble into neuritic plaques. The most toxic form of Aβ is thought to be oligomeric. A recent study reveals the cellular prion protein, PrP^C, to be a receptor for Aβ oligomers. Aβ oligomers suppress LTP signal in murine hippocampal slices but activity remains when pretreated with the PrP monoclonal anti-PrP antibody, 6D11. We hypothesized that targeting of PrP^C to prevent Aβ oligomer-related cognitive deficits is a potentially novel therapeutic approach. APP/PS1 transgenic mice aged 8 months were intraperitoneally (i.p.) injected with 1 mg 6D11 for 5 days/week for 2 weeks. Two wild-type control groups were given either the same 6D11 injections or vehicle solution. Additional groups of APP/PS1 transgenic mice were given either i.p. injections of vehicle solution or the same dose of mouse IgG over the same period. The mice were then subjected to cognitive behavioral testing using a radial arm maze, over a period of 10 days. At the conclusion of behavioral testing, animals were sacrificed and brain tissue was analyzed biochemically or immunohistochemically for the levels of amyloid plaques, PrP^C, synaptophysin, Aβ40/42 and Aβ oligomers.     

Expression of ionotropic glutamate receptors in the retina of the rdta transgenic mouse

Background  

The expression of retinal CaMKII is up-regulated in the retina of the rdta mouse in which rod photoreceptors are genetically ablated. As ionotropic glutamate receptors are known substrates of CAMKII, this study set out to determine if the protein levels of ionotropic glutamate receptors in the rdta mouse retina are also affected.     

Evaluation of a recombinant human gelatin as a substitute for a hydrolyzed porcine gelatin in a refrigerator-stable Oka/Merck live varicella vaccine

Background  

The labile nature of live, attenuated varicella-zoster virus (Oka/Merck) requires robust stabilization during virus bulk preparation and vaccine manufacturing in order to preserve potency through storage and administration. One stabilizing ingredient used in a varicella-zoster virus (VZV) vaccine is hydrolyzed porcine gelatin which represents the major protein/peptide-based excipient in the vaccine formulation.     

Molecular characterization and temporal expression profiling of presenilins in the developing porcine brain

Background  

The transmembrane presenilin (PSEN) proteins, PSEN1 and PSEN2, have been proposed to be the catalytic components of the γ-secretase protein complex, which is an intramembranous multimeric protease involved in development, cell regulatory processes, and neurodegeneration in Alzheimer's disease. Here we describe the sequencing, chromosomal mapping, and polymorphism analysis of PSEN1 and PSEN2 in the domestic pig (Sus scrofa domesticus).     

Evidence for a wide extra-astrocytic distribution of S100B in human brain

Background  

S100B is considered an astrocytic in-situ marker and protein levels in cerebrospinal fluid (CSF) or serum are often used as biomarker for astrocytic damage or dysfunction. However, studies on S100B in the human brain are rare. Thus, the distribution of S100B was studied by immunohistochemistry in adult human brains to evaluate its cell-type specificity.     

An over-expression system for characterizing <Emphasis Type="Italic">Ppt1</Emphasis> function in <Emphasis Type="Italic">Drosophila</Emphasis>

Background  

The infantile onset form of Neuronal Ceroid Lipofuscinoses (INCL) is the earliest and most severe form of NCL, with neurological symptoms that reflect massive neurodegeneration in the CNS and retina. INCL is due to recessively inherited mutations at the CLN1 locus. This locus encodes the evolutionarily conserved enzyme palmitoyl-protein thioesterase 1 (PPT1), indicating an essential role for protein palmitoylation in normal neuronal function.     

Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats

Background  

Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism.