cytoplasm, dendrite, dendritic shaft, glutamatergic synapse, membrane, neuron spine, plasma membrane, postsynaptic density, postsynaptic membrane, glutamate receptor binding
May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons.
Link to Pubmed [PMID] - 28275106. Open Biol 2017 03;7(3). The disrupted-in-schizophrenia 1 () gene was identified as a genetic risk factor for chronic mental illnesses (CMI) such as schizophrenia, bipolar disorder and severe recurrent depression. Insoluble aggregated DISC1 variants were found in the cingular cortex of sporadic, i.e. non-genetic, CMI patients. This suggests protein pathology as a novel, additional pathogenic mechanism, further corroborated in a recent transgenic rat model presenting DISC1 aggregates. Since the potential role of aggregation of DISC1 in sporadic CMI is unknown, we investigated whether DISC1 undergoes aggregation in cell culture and could spread between neuronal cells in a prion-like manner, as shown for amyloid proteins in neurodegenerative diseases. Co-culture experiments between donor cells forming DISC1 aggregates and acceptor cells showed that 4.5% of acceptor cells contained donor-derived DISC1 aggregates, thus indicating an efficient transfer DISC1 aggregates ...
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Isolation of the PSD fraction. PSD fractions were prepared from rat forebrains as previously described (Carlin et al., 1980; Cho et al., 1992). Synaptosomes were isolated from homogenates by differential and density gradient centrifugation and then extracted with 0.5% Triton X-100 for 15 min. The resulting "One-Triton" PSD fraction was pelleted by centrifugation at 36,800 × gfor 45 min. A portion of the One-Triton fraction was extracted again either with 0.5% Triton X-100 for 15 min or with 3%N-lauroyl-sarcosine for 10 min and then pelleted by centrifugation at 201,800 × g for 1 hr to obtain the "Two-Triton" PSD fraction or the "One-Triton plus Sarcosyl" PSD fraction, respectively. Protein concentrations were determined by a modified method of Lowrey (Peterson, 1983).. Identification of proteins in the PSD fraction by mass spectrometry. Protein identification was performed by mass spectrometry combined with sequence database searches (Jensen et al., 1998). Protein bands cut from a Coomassie ...
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Comrade is a loaded word. Tongzhi, literally "same aspiration," was the appropriate term of address for an entire generation of Chinese, from influential Party officials and generals to ordinary mothers, street-sweepers, and butchers. Its usage signified membership in a shared, Communist dream of equality and progress. Sometime in the late-80s, tongzhi took on a secondary meaning for a less public community. It began to mean "gay.". Unlike many linguistic changes, this shift was deliberate. The new connotation was proposed by Edward Lam, one of the artist-activists who organized the first Hong Kong Gay and Lesbian Film Festival in 1989. In borrowing and reshaping tongzhi, with its suggestion of unity and shared purpose, they hoped to bring gay Chinese people out of the shadows and into the broader community. That same year, the Tiananmen protests began. Then the Berlin Wall collapsed. Tongzhi took off, but the broader community it once symbolized had fallen apart. You have to wonder if ...
TY - JOUR. T1 - Phosphorylation of CRMP2 (Collapsin Response Mediator Protein 2) is Involved in Proper Dendritic Field Organization. AU - Yamashita, Naoya. AU - Ohshima, Toshio. AU - Nakamura, Fumio. AU - Kolattukudy, Papachan. AU - Honnorat, Jérôme. AU - Mikoshiba, Katsuhiko. AU - Goshima, Yoshio. PY - 2012/1/25. Y1 - 2012/1/25. N2 - Collapsin response mediator proteins (CRMPs) are intracellular proteins that mediate signals for several extracellular molecules, such as Semaphorin3A and neurotrophins. The phosphorylation of CRMP1 and CRMP2 by Cdk5 at Ser522 is involved in axonal guidance and spine development. Here, we found that the Ser522-phosphorylated CRMP1 and/or CRMP2 are enriched in the dendrites of cultured cortical neurons and P7 cortical section. To determine the physiological role of CRMPs in dendritic development, we generated CRMP2 knock-in mutant mice (crmp2ki/ki) in which the Ser residue at 522 was replaced with Ala. Strikingly, the cortical basal dendrites of double mutant ...
TY - JOUR. T1 - Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency. AU - Calingasan, Noel Y.. AU - Gandy, Samuel E.. AU - Baker, Harriet. AU - Sheu, Kwan Fu Rex. AU - Smith, Jonathan D.. AU - Lamb, Bruce T.. AU - Gearhart, John D.. AU - Buxbaum, Joseph D.. AU - Harper, Clive. AU - Selkoe, Dennis J.. AU - Price, Donald L.. AU - Sisodia, Sangram S.. AU - Gibson, Gary E.. PY - 1996/9/1. Y1 - 1996/9/1. N2 - Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in abnormal neurites and perikarya along the periphery of, or scattered within, the lesion. Prompted by these data and our ...
Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied. We investigated the clinicopathological features of PMLP and the significance of CRMP4 methylation in PMLP. The clinical data and diagnosis information of 10 patients with PMLP were retrospectively analyzed. The CRMP4 promotor methylation level in paraffin-embedded tissues of the 10 patients with PMLP were determined and then compared to limited prostate cancer (LPCa) and its negative lymph node tissue [LPCa-LN (−) (10 cases)] and also to metastatic prostate
TY - JOUR. T1 - Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice. AU - Sheng, Guoqing. AU - Xu, Xingshun. AU - Lin, Yung Feng. AU - Wang, Chuan En. AU - Rong, Juan. AU - Cheng, Dongmei. AU - Peng, Junmin. AU - Jiang, Xiaoyan. AU - Li, Shi Hua. AU - Li, Xiao Jiang. PY - 2008/8/1. Y1 - 2008/8/1. N2 - Joubert syndrome is an autosomal recessive disorder characterized by congenital malformation of the cerebellum and brainstem, with abnormal decussation in the brain. Mutations in the Abelson helper integration site 1 gene, which encodes the protein AHI1, have been shown to cause Joubert syndrome. In this study, we found that mouse Ahi1 formed a stable complex with huntingtin-associated protein 1 (Hap1), which is critical for neonatal development and involved in intracellular trafficking. Hap1-knockout mice showed significantly reduced Ahi1 levels, defective cerebellar development, and abnormal axonal decussation. Suppression of Ahi1 also ...
Cocaine- and amphetamine-regulated transcript-immunoreactive (CART-IR) neurons and nerve fibers were abundant in the submucosal and myenteric plexuses of t
The collapsin response mediator protein (CRMP) family of intracellular phosphoproteins are predominantly expressed in the nervous system during development. These proteins play important roles in axon formation from neurites, and in neuron guidance, growth, and polarity. CRMP-2 is encoded by the DPYSL2 gene in humans. It is also known as dihydropyrimidinase-like 2 (DRP2), dihydropyrimidinase-related protein 2 (DHPRP2), unc-33-like phosphoprotein 2 (ULIP2), and N2A3. CRMP-2 promotes microtubule assembly and is required for growth cone collapse. It also plays a role in synaptic signaling through interactions with calcium channels. Mutations in the DPYSL2 gene have been implicated in multiple neurological disorders. A hyperphosphorylated form of CRMP-2 may play a key role in the development of Alzheimers disease.. ...
The collapsin response mediator protein (CRMP) family of intracellular phosphoproteins are predominantly expressed in the nervous system during development. These proteins play important roles in axon formation from neurites, and in neuron guidance, growth, and polarity. CRMP-2 is encoded by the DPYSL2 gene in humans. It is also known as dihydropyrimidinase-like 2 (DRP2), dihydropyrimidinase-related protein 2 (DHPRP2), unc-33-like phosphoprotein 2 (ULIP2), and N2A3. CRMP-2 promotes microtubule assembly and is required for growth cone collapse. It also plays a role in synaptic signaling through interactions with calcium channels. Mutations in the DPYSL2 gene have been implicated in multiple neurological disorders. A hyperphosphorylated form of CRMP-2 may play a key role in the development of Alzheimers disease.. ...
NUB1 suppression of Huntington toxicity: mechanistic insights Yao Yao, Boxun Lu Department of Biophysics, School of Life Sciences, Fudan University, Shanghai, Peopleâ s Republic of China Abstract: Huntingtonâ s disease (HD) is an autosomal dominant neurodegenerative disorder marked by chorea, dystonia, incoordination, and cognitive and motor disturbance. The major cause of HD is the cytotoxicity of the mutant huntingtin protein (mHTT), encoded by the mutant HTT gene. The mechanism by which mHTT leads to cytotoxicity and neuronal death is unclear, and thus enhancing clearance of the mHTT protein is likely to be an effective approach to treat HD. We have recently identified NUB1 (negative regulator of ubiquitin-like proteins 1) as a modifier of mHTT levels via enhancement of its proteasomal degradation. In this review, we will discuss the mechanism of NUB1-mediated mHTT clearance and potential targeting strategies. Keywords: drug target discovery, Huntingtonâ s disease, NEDD8, ubiquitination
Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Collapsin response mediator protein 3 increases the dendritic arborization of is vidalista 10 generic cialis buy online hippocampal neurons. Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with perindopril. A ...
Title: Increased CRMP2 Phosphorylation is Observed in Alzheimers Disease; Does this Tell us Anything About Disease Development?. VOLUME: 6 ISSUE: 3. Author(s):M. P.M. Soutar, P. Thornhill, A. R. Cole and C. Sutherland. Affiliation:Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, United Kingdom.. Abstract: Collapsin response mediator protein-2 (CRMP2) was recently identified as a physiological substrate for GSK3 and Cdk5, two protein kinases suggested to exhibit greater activity in Alzheimer s disease (AD). Indeed, phosphorylation of CRMP2, at the residues targeted by GSK3 and Cdk5, is relatively high in cortex isolated from human AD brain, as well as in the brains of animal models of AD, while phospho-CRMP2 is found in neurofibrillary tangles. In mouse models of AD, increased phosphorylation occurs prior to pathology. Although CRMP2 has no known enzymatic activity, a great deal of information is appearing on its importance in neuronal ...
Background and purpose: Glia maturation factor (GMF), a brain specific protein, discovered and characterized in our laboratory, induces expression of proinflammatory cytokines/ chemokines in the central nervous system (CNS). Recently, it has been demonstrated that deficiency of GMF mitigates neuronal damage in tissue culture cell and animal models of neurodegeneration. Since, GMF expression in brain enhances inflammation; we tested the hypothesis that deficiency of GMF abrogates the inflammatory responses in experimental model of ischemic stroke.. Methods: Transient focal cerebral ischemia was induced by 1 hour of occlusion of the right middle cerebral artery (MCAO) with a 7.0 monofilament in GMF-containing wild type (Wt) and GMF-deficient (GMF-KO) mice. Mice were anesthetized with 1-1.5% isoflurane mixed with medical oxygen. Body temperature was maintained at 37°C ± 1.0 using a heating pad. At 23 hours after ischemia/reperfusion, mice were tested for neurological scores and were sacrificed ...
DRP-2, also known as collapsin response mediator protein-2 (CRMP-2), is expressed at high levels in the developing nervous system and plays a critical…
A novel gene therapy drug developed by antibody company Vybion has been shown to block cellular gene dysregulation and delay cognitive and motor problems associated with Huntingtons disease. The details of the intrabody drug INT41, an antibody that binds to an intracellular protein, were published in the Journal of Neurodegenerative Diseases.. INT41 prevents toxic N-terminal huntingtin fragments from being transported into the nucleus of the cell and blocks them from binding with the DNA. The drug was tested in the well-validated R6/2 mouse model of Huntingtons disease.. "We believe that our therapeutic approach to the treatment of Huntingtons disease has provided a biological rationale linking Huntingtons disease progression and toxic N-terminal fragments," said Dr. Lee Henderson, CEO of Vybion. "We look forward to completing our plans for human patient trials.". The drug candidate is currently in late-stage preclinical development for the treatment of Huntingtons disease. Vybions ...
Huntingtons disease (HD) is caused by an abnormal expansion of a polyglutamine (polyQ) tract within the Huntingtin (Htt) protein. Recent studies have demonstra...
Huntingtons disease (HD) is an autosomal dominant, progressive neurodegenerative disease caused by an expanded polyglutamine (polyQ) tract in the N-terminal region of mutant huntingtin (mHtt). As a result, mHtt forms aggregates that are abundant in the nuclei and processes of neuronal cells. Although the roles of mHtt aggregates are still debated, the formation of aggregates points to deficient clearance of mHtt in brain cells. Since the accumulation of mHtt is a prerequisite for its neurotoxicity, exploring the mechanisms for mHtt accumulation and clearance would advance our understanding of HD pathogenesis and help us develop treatments for HD. We know that the ubiquitin-proteasome system and autophagy play important roles in clearing mHtt; however, how mHtt preferentially accumulates in neuronal nuclei and processes remains unclear. Studying the clearance of mHtt in neuronal cells is a challenge because neurons are morphologically and functionally polarized, which means the turnover of mHtt may be
Manhasset, NY - Investigators at The The Feinstein Institute for Medical Research have discovered a new way to measure the progression of Huntingtons disease, using positron emission tomography (PET) to scan the brains of carriers of the gene. The findings are published in the September issue of The Journal of Clinical Investigation.. Huntingtons disease causes the progressive breakdown of nerve cells in the brain, which leads to impairments in movement, thinking and emotions. Most people with Huntingtons disease develop signs and symptoms in their 40s or 50s, but the onset of disease may be earlier or later in life. Medications are available to help manage the symptoms of Huntingtons disease, but treatments do not prevent the physical, mental and behavioral decline associated with the condition.. Huntingtons disease is an inherited disease, passed from parent to child through a mutation in the normal gene. Each child of a parent with Huntingtons disease has a 50/50 chance of inheriting ...
High throughput screening Scientists know that the faulty huntingtin protein causes HD, but how it kills cells is not fully known. By screening hundreds of compounds, scientists hope to find one that prevents the aggregation or cleavage of the mutant huntingtin protein - and thereby stops the cells being killed. If successful, they will try this in tissue culture, then examine the effects on animals carrying the faulty HD gene. If the results of both these are successful, the compound can be safety tested in preparation for human trials. ...
Two neuron-specific proteins, neurogranin (Ng), and neuromodulin (GAP43), were studied. Our first aim was to know the potentiality of various chemicals for their induction of Ng mRNA expression; our second one was to know the intracellular localization of GAP43 and its co-localization with calmodulin (CaM). Our results indicated that although some of the NO donors could enhance Ng promoter activity, they could not induce Ng mRNA expression in HEK293 and PC12 cells. Moreover, our findings revealed that Ng mRNA could be induced only by NGF and only in PC12 cells. For GAP43b s intracellular localization and co-localization with CaM, our results revealed DsRed-GAP43 and its mutants (S41D, S41G) were expressed mainly in the region near to cell membrane while EGFP-GAP43 and its mutants (S41D, S41G) were mostly distributed in cytoplasm. PMA treatment did not affect the localization of GAP43. For the co-transfection experiments, a particular region of co-localization of GAP43 and CaM was found to be ...
LC3-mHTT-IN-2 (Compound AN2) is a mHTT-LC3 linker compound, which interacts with both mutant huntingtin protein (mHTT) and LC3B but not with wtHTT or irrelevant control proteins. LC3-mHTT-IN-2 reduces the levels of mHTT in an allele-selective manner in cultured Huntington disease (HD) mouse neurons. - Mechanism of Action & Protocol.
These data are consistent with previous reports of intronic miRNA function, in which the miRNA regulates the same biological process as the protein encoded by the host gene.29 miR-218 may contribute to "fine-tuning" of Slit-Robo pathway genes or generate negative feedback in response to Slit gene activation. It is interesting to speculate that miR-218 may serve to repress the expression of the Robo1/2 receptors in the Slit ligand-expressing cells, thereby spatially separating ligand from receptor. Because Robo4 is not a target of miR-218 regulation, it also is possible that miR-218 affects the ratio of Robo1/2 and Robo4 proteins, thereby influencing vascular patterning.. It is currently debated whether the Robo1 and -2 receptors provide a positive or negative influence on EC migration, although Robo4 is generally thought of as a repulsive or stabilizing cue during vascular pathfinding.9,37 In our hands, it appears that repression of Robo1/2 and HSPG biosynthetic molecules by miR-218 negatively ...
Provided herein are methods, compounds, and compositions for reducing expression of huntingtin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate Huntingtons disease, or a symptom thereof.
We designed ISIS-HTTRx to target the huntingtin gene and reduce the production of huntingtin protein, which is the known cause of the disease," stated Frank Bennett, Ph.D., the Isis senior vice president for research. "This approach has the potential to prevent or slow the progression of this disease. If this first-in-human trial proves the drug is safe, we look forward to continuing our successful partnership with Roche to bring the drug to market ...
I have been continuing to characterise the huntingtin protein samples I am generating in the lab. You can read about my first attempts to map post-translational modifications by mass spec here. Previously I found phosphorylation modifications on the huntingtin protein which are located on the same sites as huntingtin protein derived from human cells which Read More …. ...
Huntingtons disease is a progressive neurodegenerative disorder that affects around five people in every 100,000. It is caused by an increase in a polyglutamine region of the Huntingtin protein, resulting in a toxic gain of function mutation...
Legleiter J, Lotz GP, Miller J, Ko J, Ng C, Williams GL, Finkbeiner S, Patterson PH, Muchowski PJ. Monoclonal antibodies recognize distinct conformational epitopes formed by polyglutamine in a mutant huntingtin fragment ...
The Hereditary Disease Array Group (HDAG) today reported important new findings on Huntingtons disease, in six peer-reviewed papers published in the online version of the August 15th issue of Human Molecular Genetics. The papers are part of the HDAGs two-year research effort that brought over 50 scientists from 19 universities together to discover how the mutant Huntingtons disease gene causes brain cells to die by affecting other biological pathways.
分泌型糖蛋白Slit及其受体Robo最初作为一类重要的神经元轴突导向因子被发现。随着对Slit-Robo信号通路作用机制研究的不断深入,该信号通路还参与血管新生、肿瘤血管发生、炎症、白细胞趋化及血管渗漏等过程。
A defect in a single gene causes Huntingtons disease. Its considered an autosomal dominant disorder. This means that one copy of the abnormal gene is enough to cause the disease. If one of your parents has this genetic defect, you have a 50 percent chance of inheriting it. You can also pass it on to your children.. The genetic mutation responsible for Huntingtons disease is different from many other mutations. There isnt a substitution or a missing section in the gene. Instead, there is a copying error. An area within the gene is copied too many times. The number of repeated copies tends to increase with each generation.. In general, symptoms of Huntingtons disease show up earlier in people with a larger number of repeats. The disease also progresses faster as more repeats build up.. ...
How do you get Huntingtons disease?. Huntingtons disease is caused by a faulty gene, which is passed from parent to child. The faulty gene makes a faulty protein called huntingtin. Scientists throughout the world are working to find out exactly what this protein does.. Each person whose parent has Huntingtons disease is born with a 50-50 chance of inheriting the faulty gene on chromosome 4 . Anyone who inherits the gene will at some stage develop the disease. ...
In collaboration with Dr. Macdonald and others at CHDI, the Isis HD team is working to validate huntingtin lowering biomarkers. Beside the development of assays (investigative procedures) to measure the huntingtin protein in CSF, CHDI is also looking at PET-ligands to measure the effects of ISIS-HTTRx in the brain. The ligand, sometimes called a PET tracer, binds to a target or receptor in the brain, which can be measured in people using PET scan imaging. The team has selected ligands to targets that are altered in HD; the hope is that when huntingtin is lowered the level of these targets will be restored, indicating that ISIS-HTTRx has a desired effect ...
Commonly asked questions about Huntingtons Disease. Learn about causes, symptoms, types, stages and treatments of Huntingtons Disease. Call:(866) 280-4722
Researchers from four organizations have identified more than 200 new proteins that bind to normal and mutant forms of the protein that causes Huntingtons disease (HD). HD is a fatal inherited disease that affects 30,000 Americans annually by laying waste to their nervous system. The research was led by Buck Institute faculty member Robert E. Hughes, Ph.D.
Huntingtons disease causes a progressive breakdown of nerve cells in the brain. Find out about symptoms, diagnosis and treatment.
Researchers have found that aberrant protein aggregates responsible for Huntingtons disease have some weak spots that could be exploited to hinder the development of this pathology. The study, published on Scientific Report, has been conducted by scientists of the Centre for Complexity and Biosystems (CC&B) of the University of Milan, in collaboration with colleagues from
A shared mechanism of muscle wasting in cancer and Huntingtons disease. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Huntingtons disease can take a long time to diagnose. It is a hereditary illness with numerous symptoms that leave a person unable to walk or talk and needing full-time care. We explain genetic testing, drug treatments, and the state of research to find a cure, plus the stages of the disease and therapies available.
Researchers at the Ludwig Institute for Cancer Research at the University of California found that the proposed new drug can help silence the mutated gene responsible for Huntingtons disease.
The battle against Huntingtons disease rages on and we need you to join TEAM HOPE - VIRTUALLY! A virtual walk is a real walk, but on your terms. You get choose your own course. Now, you can take part wherever you are…from the comfort and safety of your own home, around your yard, or even your neighborhood (following social distance guidelines, of course). ...
When Marjorie Guthrie founded our organization in 1967, her vow was to "do something" about this devastating disease. Today we continue her legacy by bringing together the entire community to provide help and hope to all families affected by Huntingtons disease. Listed here are some of the ways you can get involved in the fight against HD. ...
Various new treatments for Huntingtons disease are being studied, and, although these are still at an experimental stage, researchers feel the outlook is
Global Markets Directs, Huntingtons Disease - Pipeline Review, H2 2014, provides an overview of the Huntingtons Diseases therapeutic pipeline. This report provides comprehensive
View mouse Neurog2 Chr3:127633145-127635631 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
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