Archive for the ‘Parkinsons’ Category
Wednesday, February 1st, 2012
Apoptosis is one of the best-characterized phenomena in cellular and molecular biology. Not only is it essential for successful development, but its deregulation also leads to a number of human diseases, most notably cancer. The cysteine aspartate protease (caspase) family of proteins has been studied extensively over the past several decades and found to play a pivotal role in the execution of apoptosis; caspase activation is regarded as commitment to programmed cell death. A variety of intrinsic and extrinsic stressors are capable of initiating mediated cell death, however, transduction commonly occurs via caspase activity. Initiator caspases (8, 9, 10 and 2) are activated first, generally by binding oligomeric adaptor proteins, and subsequently activate the effector caspases (3, 7 and 6) via proteolytic cleavage.
Recent research has revealed a novel role for caspases, notably caspase-8 and -3/7, in mediating neurotoxicity in response to inflammatory stimuli in microglia. Although microglia are the primary effectors of the immune response in the nervous system, numerous studies suggest that their aberrant activation contributes to neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s and multiple sclerosis. In their groundbreaking research, Burgillos, et al. show that exposure of microglia to pro-inflammatory cytokines leads to activation of caspase-3/7 and neurotoxicity associated with neurological disease. Surprisingly, they also demonstrated that inhibition of caspase-3/7 inhibited microglial activation, and that lipopolysaccharides failed to damage neighboring neurons when caspase-3/7 was abrogated chemically or with siRNA. Finally, they provide evidence that the IKK/NF-kB pathway—a canonical pro-inflammatory pathway– is also influenced by caspase-3/7 by their ability to trigger PKC-delta.
Neuronal inflammation is both a prominent cause and result of brain injury and the identification of caspase-3/7 and -8 in its etiology provides exciting new targets for potential therapies. Coupled with the advent of nano-carriers capable of traversing the blood brain barrier, caspase-3/7 could be promising substrates for novel anti-inflammatory drugs. Novus Biologicals provides several excellent antibodies to target caspase-3 and -7 (such as NB500-206 and NB500-210) that we hope will accelerate research in this field. We are committed to producing quality research materials, and look forward to learning how our caspase 3 and caspase 7 antibodies will serve the scientific community.
Burgillos MA, Deierborg T, Kavanagh E, et al. Caspase signaling controls microglia activation and neurotoxicity. Nature 2011; 472:319-324.
Tags: Casoase 7, Caspase, Caspase 10, Caspase 10 antibody, Caspase 2, Caspase 2 antibody, Caspase 3, caspase 3 antibody, Caspase 6, Caspase 6 antibody, Caspase 7 antibody, Caspase 8, Caspase 8 antibody, Caspase 9, Caspase 9 antibody, IKK, IKK antibody, Immune response, Inflammation, NFkB, NFkB antibody, PKC-delta, PKC-delta antibody
Posted in Alzheimer's, Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Apoptosis, Cancer, Immunology, Inflammation, Neurodegeneration, Neuroscience, Parkinsons | No Comments »
Wednesday, December 21st, 2011
Estrogen receptors come in the form of two distinct forms, ER alpha and ER beta. These nuclear receptors are predominantly activated by the hormone 17-beta-estradiol to control transcription of genes throughout the immune, nervous, cardiovascular, and skeletal systems. The classic signaling method of these receptors involves homo- or hetero- receptor dimerization, followed by direct binding to estrogen response elements (ERE). They can also work in concert with other transcription factors, such as SP1 and Fos/Jun, to activate genes which do not contain an ERE. Estrogen receptor over-expression is extremely common in breast cancer, where it is experienced in over 70% of cases. Anti-estrogens which block ER alpha are the stable clinical therapy for breast cancer, but have side effects and are no longer useful after prolonged treatment where cancers can become resistant. Within this group, when the anti-estrogen drug tamoxifen is used, over 70% of women benefit from its use. Newer treatments that are similar to tamoxifen, such as raloxifene and tormifene, are also common, as well as complete blocking of estrogen signaling with aromatase inihbitors, which block estrogen production. In addition to the role of ERs in morphogenesis, estrogen receptors are widely expressed throughout the brain, where estrogen acts as a trophic factor for neurons. Interestingly, the use of estrogen as a neuroprotective agent against Alzheimer’s disease, Parkinson’s disease, and stroke is currently under investigation. However, the antiapoptotic effects of estrogen in the brain, as well as its ability to downregulate proapoptotic molecules, have been shown in numerous studies.
Tags: Alzheimer's disease, Breast Cancer, c-Fos, c-Fos antibody, c-Jun, c-Jun antibody, ER alpha, ER alpha antibody, ER beta, ER beta antibody, Estrogen Receptor alpha, Estrogen Receptor alpha antibody, Estrogen Receptor beta, Estrogen Receptor beta antibody, Fos, Fos antibody, Jun antibody, Parkinson's disease, SP1, SP1 antibody
Posted in Alzheimer's, Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Apoptosis, Cancer, Neurodegeneration, Parkinsons, Transcription Regulation, Tumor | No Comments »
Wednesday, December 14th, 2011
The peroxisome proliferator-activated receptor gamma, co-activator 1 (PGC-1 alpha or PPARGC1A) gene encodes a 91 kDa nuclear protein that acts as a transcriptional co-activator involved in energy metabolism. Interaction with PPAR gamma allows it to interface with numerous transcription factors such as cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It is believed to be a master integrator between external stimuli and cellular response, in particular mitochondrial biogenesis. It is also a major factor in muscle type determination. Recent research has shown that single-nucleotide polymorphism (SNP) mutations were associated with specific meat characteristics in pigs, which may lead to improvement in pork meat quality (PMID: 21680104).
Because PGC-1 alpha is also a transcriptional co-activator of antioxidant genes, researchers have investigated the possible link between PGC-1alpha and Parkinson’s disease. Statistical analysis has shown an association between SNP mutations and the longevity and age of onset of Parkinson’s disease (PMID: 21595954).
Interestingly, the PGC-1 alpha gene is located in a region known as Human Accelerated Region 20 (HAR 20) it is one of 49 regions in the human genome that are conserved in vertebrate evolution but show striking rapid changes in human sequences, suggesting that genes located in these regions are crucial in human evolutionary divergence from other animals.
Novus Biologicals offers many different PGC-1 alpha antibodies, lysates, proteins and RNAi that are 100% guaranteed to work for your research needs.
Tags: CREB, CREB antibody, NRF1, NRF1 antibody, NRF2, NRF2 antibody, PGC-1 alpha, PGC-1 alpha antibody, PPAR gamma, PPAR gamma antibody
Posted in Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Lipid & Metabolism, Neurodegeneration, Parkinsons, Transcription Regulation | No Comments »
Thursday, November 10th, 2011
Embryonic stem (ES) cells are cells derived from the inner cell mass of the blastocyst, an early-stage embryo. ES cells are distinguished from other cells due to their pluripotency, which is the ability to differentiate into any different type of cell in the body, and also their capability of propagating indefinitely. These two factors make embryonic stem cells valuable tools in the scientific community, especially in regenerative medicine.
Sox2 and Oct4 are well known transcriptional activators that play a crucial role in the regulation of embryonic stem cell pluripotency. When Oct4 and Sox2 expression is knocked down, embryonic stem cells lose the ability to maintain their pluripotency. Research using gene-knockout experiments has shown the importance of Oct4 and Sox2 in early embryonic development.
Oct4 and Sox2 bind to a few thousand regulatory sites in the embryonic stem cell genome, and it is likely these target genes play a role in modulating ES cell differentiation. One well known gene that is activated by Oct4 and Sox2 is Nanog. Nanog, along with Oct4 and Sox2, are core transcription factors which regulate the pluripotency and self-renewal of embryonic stem cells.
In addition to helping understand the pluripotency of ES cells, antibodies against Oct4, Sox2 and Nanog have been used to investigate malignancy in human glioma cells. Recently, there have been a number of studies focusing on the expression Oct4, Sox2 and Nanog in human gliomas. More and more research is being done to uncover the role these core regulatory factors play in glioma progression and malignancy. Huge strides have been made in stem cell-related research using Oct4, Sox2 and Nanog antibodies. This research has shown great potential for discovering treatments and cures for a wide array of diseases including cancer, Parkinson’s, Alzheimer’s and diabetes.
Tags: Embryonic Stem Cell Marker, NANOG, Nanog antibody, OCT4, Oct4 antibody, pluripotent, Sox2, Sox2 antibody
Posted in Alzheimer's, Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Cancer, Diabetes, Lipid & Metabolism, Neurodegeneration, Parkinsons, Stem Cells | No Comments »
Monday, July 11th, 2011
Ubiquitin is a small, highly conserved protein which plays an important role in protein breakdown, covalently bonding to proteins to mark them for proteolytic degradation in a process called ubiquitination. Ubiquitin also binds to inclusion bodies (accumulations of protein) in pathological conditions such as Parkinson’s and Alzheimer’s disease. Ubiquitin antibody products are therefore useful for identifying inclusions in neuroscience research.
The Ubiquitin Proteasome Pathway, or UPP, is the principal method for protein degradation in normal cells, and central to the regulation of many cellular processes, including apoptosis; biogenesis; cell division; DNA transcription; cellular differentiation; modulation of ion channels, and DNA repair. Defects in the pathway have been linked to a number of important human diseases.
Protein degradation takes place in two stages: the protein is first covalently tagged by binding to multiple ubiquitin molecules, in a process known as conjugation, before being degraded by the 26S proteasome. Covalent linkage occurs as both single molecules and poly-ubiquitin chains, with the protein binding to lysine residues on the target protein via a series of enzymatically-controlled steps. Research with ubiquitin antibodies has shown the protein can also be conjugated to itself, resulting in diverse chain linkages. Initially, the protein was thought to play a “housekeeping” role, regulating antigenic-peptide generation and protein turnover. However, recent ubiquitin antibody studies have identified non-degenerative roles in, for example, endocytosis and DNA repair.
Ubiquitin antibodies are widely used in immunohistochemistry to identify abnormal protein inclusions. These include the neurofibrillary tangles of Alzheimer’s disease; Lewy bodies of Parkinson’s disease; Mallory bodies in alcoholic liver disease and Pick disease Pick bodies. The ubiquitin antibody can also identify the Rosenthal fibers of astrocytes.
Tags: 26S Proteasome, Antibodies, Biogenesis, Housekeeping gene, Protein Turnover, Ubiquitin, ubiquitin antibody, Ubiquitin Proteasome Pathway
Posted in Alzheimer's, Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Apoptosis, DNA Repair, Neurodegeneration, Neuroscience, Parkinsons | No Comments »
Friday, May 6th, 2011
Brain-derived neurotrophic factor (BDNF) is a member of the NGF family of neurotrophins. During development it regulates the survival and differentiation of neuronal cell populations in the central and peripheral nervous system, while in adult synapses it is a major regulator of development, plasticity and transmission. We at Novus Biologicals are a leading antibody supplier for neurological research, with an extensive range of BDNF antibodies.
BDNF, like NGF, is a non-covalently linked homodimer, with an identical amino acid sequence in all known mature mammals. It is expressed at high levels in the hippocampus, cerebellum, placenta and fetal eye, and to a lesser extent in the pituitary gland, lung, spinal cord and skeletal and cardiac muscle.
BDNF plays an important role in adaptive neuronal responses, including long-term potentiation and depression, and short-term synaptic plasticity. It also plays a role in homeostasis, regulating intrinsic neuronal excitability. BDNF expression may be altered by such things as stress, seizures, ischemia and hypoglycemia. Modified BDNF expression has been linked to neuropathological disorders such as depression, Alzheimer’s, epilepsy and Parkinson’s disease.
Recent BDNF antibody studies have concentrated on activity-dependent changes (ADCs) to BDNF expression following synaptic transmission. ADCs are dependent on calcium influx, which induces transcription factors to bind nuclear calcium-response elements (CaREs).
In 2008, BDNF antibody research by Hong, et al. showed that activity-dependent BDNF expression was linked to CaRE expression and synaptic plasticity [PMID: 19038219]. In 2009, Kuczewski, et al. suggested BDNF functions as a target-derived messenger for activity-dependent synaptic plasticity [PMID: 19704877]. These experiments were dependent on products of the highest quality, supplied by leading antibody suppliers like Novus Biologicals.
Tags: Alzheimer's, Antibodies, BDNF, BDNF Antibody, Neuroscience
Posted in Alzheimer's, Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Neurodegeneration, Neuroscience, Parkinsons | No Comments »
Monday, March 21st, 2011
The glyceraldehyde 3-phosphate dehydrogenase, or GAPDH enzyme plays an important role in the conversion of glucose for energy, catalyzing the sixth step of the glycolytic pathway. A common and widely expressed protein, GAPDH mRNA is often used as a standard in mRNA studies. GAPDH antibody products are also used as a loading control in Western blot assays. We at Novus Biologicals have 55 GAPDH antibody products on our antibody database.
GAPDH catalyses the reversible oxidative phosphorylation of glyceraldehyde 3-phosphate, yielding D-glycerate 1, 3-bisphosphate in a two-step process which couples phosphorylation to oxidation. Recent GAPDH antibody studies have suggested GAPDH also has a role to play in several non-metabolic processes, including transcription activation, ER to Golgi vessel shuttling and apoptosis. GAPDH is known to bind to a number of other proteins, including the amyloid precursor protein, mutations of which can cause Alzheimer’s disease.
In 2003, Zheng, et al. identified a transcriptional role for GAPDH, forming part of the OCA-S Oct-1 coactivator complex in combination with lactate dehydrogenase. It this study, GAPDH directly bound to Oct-1, and selectively bound to the H2B promoter during the S-phase. Other GAPDH antibody studies have suggested GAPDH plays a role in basal RNA polymerase II transcription, and also DNA repair.
In 2005, Hara, et al. showed that GAPDH initiates apoptosis in response to cellular stress, binding to the E3-ubiquitin ligase Siah1 following S-nitrosylation. In 2006, the same group showed that Deprenyl, a drug used to treat Parkinson’s disease, blocked S-nitrosylation of GAPDH, preventing Siah1 binding.
Neurodegeneration and apoptosis are closely intertwined. The GAPDH antibody database may turn out to be a useful tool in the fight against neurodegenerative disorders such as Alzheimer’s, Huntington’s and Parkinson’s disease.
Tags: GAPDH, GAPDH antibody, Glucose metabolism, Glycolysis, Housekeeping gene, Huntington's Disease, Loading control
Posted in Alzheimer's, Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Apoptosis, DNA Repair, Parkinsons, Support Products | No Comments »
Monday, March 14th, 2011
Identified almost two centuries ago, Parkinson’s disease is a neurodegenerative disorder that afflicts an estimated 4-6 million worldwide (www.parkinsons.org). The prevalence of Parkinson’s disease is expected to grow considerably as the average age of the population in developed countries increases. Despite the hundreds of millions of dollars devoted annually to Parkinson’s research, there is relatively little known about the disease and its treatment. For instance, there is currently no test available to clearly identify the disease, no single environmental or genetic factor proven to cause it, and no known cure for those affected. Therefore, Parkinson’s research will continue to be an important and growing research area in the foreseeable future. Novus Biologicals offers a number of excellent immunological tools for Parkinson’s studies, particularly including our LRRK2 antibodies and Parkin antibodies.
Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin, is a leucine-rich repeat kinase family member. LRRK2 is localized in the cytoplasm and is associated with cellular membrane structures and with the mitochondrial outer membrane. Mutations in the LRRK2 gene have been associated with Parkinson’s disease, as four LRRK2 gene variants are commonly found in a third of all Parkinson’s cases. Novus Biologicals Rabbit Polyclonal LRRK2 antibody (catalog number NB300-268) may be used in Western blot and immunoprecipitation as well as immunofluorescent staining on tissues and cultured cells from human, mouse and bovine. This LRRK2 antibody has been thoroughly tested and has currently been referenced in seven published journal articles.
Parkin (PARK2) is a component of a multiprotein E3 ubiquitin ligase complex which in turn is part of the ubiquitin-proteasome system that catalyzes the covalent attachment of ubiquitin moieties onto substrate proteins for degradation. Mutations in this gene are known to cause a familial form of Parkinson’s disease known as autosomal recessive juvenile Parkinson disease. Novus Biologicals rabbit polyclonal Parkin antibody (catalog number R-114-100) may be used in Western blot and immunohistochemical staining of human and rat samples. At this time, the Parkin antibody has been thoroughly characterized and cited in eight published articles.
Novus provides a variety of antibodies for the research of neurodegenerative conditions, including Parkinson’s, Alzheimer’s disease and more. Please feel free to browse all of our quality guaranteed neuroscience antibodies here.
Tags: LRRK2, LRRK2 antibody, Parkin, Parkin antibody
Posted in Alzheimer's, Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Neurodegeneration, Neuroscience, Parkinsons | No Comments »
Friday, August 27th, 2010
E3 ubiquitin ligases are standards in most antibody catalogs. These proteins are essential to the process of ubiquitination, which is expressed in protein pathways throughout the body and is often linked to disease states. It is widely used as a biomarker, with ubiquitin antibodies being widely used to identify the protein accumulations (inclusion bodies) which occur in conditions such as Alzheimer’s, Parkinson’s and Huntington’s disease.
The E3 ligases target specific proteins and are important in apoptosis and proteolysis. Their function is generally to assist polyubiquitination – the binding of multiple ubiquitin molecules to the same target protein – which is the signal for degradation (i.e. destruction) by the proteasome to begin. In combination with an E2 ubiquitin-conjugating enzyme, E3 ligases trigger the attachment of ubiquitin to lysine on their target proteins, via isopeptide bonding. Further ubiquitin molecules are then attached, one to the next.
The IBR (In Between Ring fingers) family of proteins are so-called because of a specific domain, found between pairs of ring fingers. Other names include C6HC and DRIL (double ring finger linked) domain. Also called RBR proteins, they are found in all eukaryotic organisms. They are thought to play an indirect role in regulating DNA transcription and protein quality control.
In recent times, it has been discovered that IBR-type ligases play a part in ubiquitination, often forming part of cullin-containing ubiquitin ligase complexes. Mutated forms of the Parkin IBR ligase is known to be expressed in familial forms of Parkinson’s disease. Recently, IBRDC2, one of the IBR-type E3 ubiquitin ligases covered by our antibody database at Novus Biologicals, has been suspected of regulating apoptosis and Bax activation.
Tags: Antibodies, antibody catalogue, Antibody database, Antibody suppliers, IBRDC2, IBRDC2 antibody, Ubiquitin, ubiquitin antibody, Ubiquitin Proteasome Pathway
Posted in Alzheimer's, Antibodies, Antibody catalog, Antibody database, Antibody suppliers, Apoptosis, Neurodegeneration, Neuroscience, Parkinsons | No Comments »
