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Brain Proteins (brain + protein)
Selected AbstractsNeuropathology, biochemistry, and biophysics of ,-synuclein aggregationJOURNAL OF NEUROCHEMISTRY, Issue 1 2007Vladimir N. Uversky Abstract Aggregation of ,-synuclein, an abundant and conserved pre-synaptic brain protein, is implicated as a critical factor in several neurodegenerative diseases. These diseases, known as synucleinopathies, include Parkinson's disease, dementia with Lewy bodies (LBs), diffuse LB disease, the LB variant of Alzheimer's disease, multiple system atrophy, and neurodegeneration with brain iron accumulation type I. Although the precise nature of in vivo,-synuclein function remains elusive, considerable knowledge has been accumulated about its structural properties and conformational behavior. ,-Synuclein is a typical natively unfolded protein. It is characterized by the lack of rigid, well-defined, 3-D structure and possesses remarkable conformational plasticity. The structure of this protein depends dramatically on its environment and it accommodates a number of unrelated conformations. This paper provides an overview of the biochemistry, biophysics, and neuropathology of ,-synuclein aggregation. [source] Pathological biochemistry of ,-synucleinopathyNEUROPATHOLOGY, Issue 5 2007Takeshi Iwatsubo Lewy bodies (LBs) are hallmark lesions in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We raised a monoclonal antibody LB509 against purified LBs from the brains of patients with DLB that strongly immuolabled LBs, and found that ,-synuclein is one of the major components of LBs. Thus, the deposition of ,-synuclein, an abundant presynaptic brain protein, as fibrillary aggregates in affected neurons or glial cells, was highlighted as a hallmark lesion of a subset of neurodegenerative disorders, including PD, DLB and multiple system atrophy collectively referred to as synucleinopathies. Importantly, the identification of missense mutations in and multiplication of ,-synuclein gene in some pedigrees of familial PD has strongly implicated ,-synuclein in the pathogenesis of PD and other synucleinopathies. We then examined the specific post-translational modifications that characterize and underlie the aggregation of ,-synuclein in synucleinopathy brains by mass spectrometry and using a specific antibody, and found that serine 129 of ,-synuclein deposited in synucleinopathy lesions is selectively and extensively phosphorylated. Furthermore we generated transgenic C. elegans overexpressing ,-synuclein in neurons, and found that overexpression of familial PD-linked mutant form of ,-synuclein impairs functions of dopamine neurons. These findings collectively underscore the importance of deposition of ,-synuclein as well as its phosphorylation in the pathogenesis of ,-synucleinopathies. [source] Stimulation of protein biosynthesis in rat hepatocytes by extracts of Momordica charantiaPHYTOTHERAPY RESEARCH, Issue 2 2001O. O. Oyedapo Abstract The in vivo effect of the administration of extracts of Momordica charantia on certain biochemical parameters of Sprague-Dawley rats was investigated. It was observed that there was an increase in muscle and liver protein levels, while there was a reduction in the levels of brain protein, muscle and liver glycogen. The activities of plasma L -alanine transaminase and alkaline phosphatase were reduced. The L -aspartate transaminase and adenosine triphosphatase activities were slightly elevated in whole plant extract treated rats while the L -aspartate transaminase was unaffected by the ethanol extract but reduced the adenosine triphosphatase activity. Copyright © 2001 John Wiley & Sons, Ltd. [source] Highly sensitive and simple fluorescence staining of proteins in sodium dodecyl sulfate-polyacrylamide-based gels by using hydrophobic tail-mediated enhancement of fluorescein luminescenceELECTROPHORESIS, Issue 19-20 2003Chulhun Kang Abstract Fluorescein has an extremely low luminescence intensity in acidic aqueous media. However, when it was bound to proteins, subsequent increase of luminescence intensity took place. Furthermore, when a hydrophobic tail, such as aliphatic hydrocarbons, was introduced to fluorescein, more dramatic increase of luminescence intensity was observed upon binding to proteins. In the present study, by utilizing this luminescence enhancement, three hydrophobic fluorescein dyes (5-dodecanoyl amino fluorescein, 5-hexadecanoyl amino fluorescein, and 5-octadecanoyl amino fluorescein) were examined as noncovalent fluorescent stains of protein bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Effective incorporation of the dyes to proteins in gels was accomplished either simply by adding dyes at the protein fixation step, or by treating gels with a staining solution after the fixation. The sensitivity of this staining method using the fluorescein derivatives was approximately 1 ng/band for most proteins. For some cases, protein bands containing as low as 0.1 ng were successfully visualized. In addition, the detection sensitivity showed much less protein-to-protein variation than silver staining. This new staining method was also successfully applied to two-dimensional electrophoresis of rat brain proteins. Its overall sensitivity was comparable to that of silver staining. [source] Impairment of conditioned freezing to tone, but not to context, in Fyn-transgenic mice: relationship to NMDA receptor subunit 2B functionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2005N. Kojima Abstract We previously demonstrated that transgenic mice overexpressing Fyn tyrosine kinase exhibit higher seizure susceptibility and enhanced tyrosine phosphorylation of several proteins, including the N -methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B). In the present study, we analysed behavioural phenotypes, especially conditioned fear responses, of Fyn-transgenic (TG) mice to better understand the role of Fyn in learned emotional behaviour. Tone-dependent conditioned freezing was significantly attenuated in Fyn-TG mice, whereas context-dependent freezing was unaffected. Neither massed nor spaced conditioning ameliorated the attenuation of tone-dependent freezing. However, the selective NR2B antagonist ifenprodil, when administered before conditioning, restored tone-dependent freezing in Fyn-TG mice at a dose that did not affect freezing in wild-type (WT) mice. These results suggest that impairment of tone-dependent conditioned freezing in Fyn-TG mice is caused by disruption of the NR2B-containing NMDA receptor function. Tyrosine phosphorylation of brain proteins, including NR2B, was enhanced in Fyn-TG mice compared with that in WT mice. We also found that ifenprodil significantly suppressed the enhanced tyrosine phosphorylation. Thus, our data support the notion that NMDA receptor activity is tightly correlated with protein tyrosine phosphorylation, and Fyn might be one key molecule that controls tone-dependent conditioned freezing through the regulation of NMDA receptor function. [source] ,IV tubulin is selectively expressed by oligodendrocytes in the central nervous systemGLIA, Issue 3 2005Nobuo Terada Abstract Oligodendrocyte differentiation and myelination involve dramatic changes in cell signaling pathways, gene expression patterns, cell shape, and cytoskeletal organization. In a pilot study investigating CNS angiogenesis, oligodendrocytes were intensely labeled by antisera directed against the C-terminal of Tie-2, a 140-kDa transmembrane receptor for angiopoietin. Immunoprecipitation of rat brain proteins with Tie-2 C-terminal antisera, however, produced a single spot of ,55-kDa pI ,5 by two-dimensional (2D) electrophoresis, which was identified as ,-tubulin by mass spectrometry. Isotype-specific antibodies for ,IV tubulin selectively labeled oligodendrocytes. First detected in premyelinating oligodendrocytes, ,IV tubulin was abundant in myelinating oligodendrocyte perinuclear cytoplasm and processes extending to and along developing myelin internodes. ,IV tubulin-positive MTs were diffusely distributed in oligodendrocyte perinuclear cytoplasm and not organized around the centrosome. ,IV tubulin may play a role in establishing the oligodendrocyte MT network, which is essential for the transport of myelin proteins, lipids, and RNA during myelination. © 2005 Wiley-Liss, Inc. [source] Proteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobuleJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Tanea T. Reed Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in multiple cognitive domains. Its pathological hallmarks include senile plaques and neurofibrillary tangles. Mild cognitive impairment (MCI) is the earliest detectable stage of AD with limited symptomology and no dementia. The yearly conversion rate of patients from MCI to AD is 10,15%, although conversion back to normal is possible in a small percentage. Early diagnosis of AD is important in an attempt to intervene or slow the advancement of the disease. Early AD (EAD) is a stage following MCI and characterized by full-blown dementia; however, information involving EAD is limited. Oxidative stress is well-established in MCI and AD, including protein oxidation. Protein nitration also is an important oxidative modification observed in MCI and AD, and proteomic analysis from our laboratory identified nitrated proteins in both MCI and AD. Therefore, in the current study, a proteomics approach was used to identify nitrated brain proteins in the inferior parietal lobule from four subjects with EAD. Eight proteins were found to be significantly nitrated in EAD: peroxiredoxin 2, triose phosphate isomerase, glutamate dehydrogenase, neuropolypeptide h3, phosphoglycerate mutase1, H+, transporting ATPase, ,-enolase and fructose-1,6-bisphosphate aldolase. Many of these proteins are also nitrated in MCI and late-stage AD, making this study the first to our knowledge to link nitrated proteins in all stages of AD. These results are discussed in terms of potential involvement in the progression of this dementing disorder. [source] BDNF and the diseased nervous system: a delicate balance between adaptive and pathological processes of gene regulationJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Yinghui Hu Abstract It is clear that brain-derived neurotrophic factor (BDNF) plays a crucial role in organizing the response of the genome to dynamic changes in the extracellular environment that enable brain plasticity. BDNF has emerged as one of the most important signaling molecules for the developing nervous system as well as the impaired nervous system, and multiple diseases, such as Alzheimer's, Parkinson's, Huntington's, epilepsy, Rett's syndrome, and psychiatric depression, are linked by their association with potential dysregulation of BDNF-driven signal transduction programs. These programs are responsible for controlling the amount of activated transcription factors, such as cAMP response element binding protein, that coordinate the expression of multiple brain proteins, like ion channels and early growth response factors, whose job is to maintain the balance of excitation and inhibition in the nervous system. In this review, we will explore the evidence for BDNF's role in gene regulation side by side with its potential role in the etiology of neurological diseases. It is hoped that by bringing the datasets together in these diverse fields we can help develop the foundation for future studies aimed at understanding basic principles of gene regulation in the nervous system and how they can be harnessed to develop new therapeutic opportunities. [source] Altered glycosylation of acetylcholinesterase in Creutzfeldt,Jakob diseaseJOURNAL OF NEUROCHEMISTRY, Issue 1 2006Marķa-Ximena Silveyra Abstract Changes in the glycosylation pattern of brain proteins have been associated with Creutzfeldt,Jakob disease (CJD). We have investigated the glycosylation status of acetylcholinesterase (AChE) by lectin binding assay. Our data show that in lumbar CSF from definite and probable sporadic CJD cases AChE activity is lower compared with that in age-matched controls. We also show, for the first time, that AChE glycosylation is altered in CJD CSF and brain. Unlike Alzheimer's disease, in which an alteration in both the glycosylation and levels of AChE molecular forms is observed, the abnormal glycosylation of AChE in CJD appears to be unrelated to changes in molecular forms of this enzyme. These findings suggest that altered AChE glycosylation in CJD may be a consequence of the general perturbation of the glycosylation machinery that affects prion protein, as well as other proteins. The diagnostic potential of these changes remains to be explored. [source] Developmental vitamin D deficiency alters brain protein expression in the adult rat: Implications for neuropsychiatric disordersPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2007Lionel Almeras Abstract An increased risk for multiple sclerosis and schizophrenia is observed at increasing latitude and in patients born in winter or spring. To explore a possible link between maternal vitamin D deficiency and these brain disorders, we examined the impact of prenatal hypovitaminosis D on protein expression in the adult rat brain. Vitamin D-deficient female rats were mated with vitamin D normal males. Pregnant females were kept vitamin D-deficient until birth whereupon they were returned to a control diet. At week 10, protein expression in the progeny's prefrontal cortex and hippocampus was compared with control animals using silver staining 2-D gels associated with MS and newly devised data mining software. Developmental vitamin D (DVD) deficiency caused a dysregulation of 36 brain proteins involved in several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, PTMs, synaptic plasticity and neurotransmission. A computational analysis of these data revealed that (i) nearly half of the molecules dysregulated in our animal model have also been shown to be misexpressed in either schizophrenia and/or multiple sclerosis and (ii) an impaired synaptic network may be a consequence of mitochondrial dysfunction. [source] Redox proteomics identification of 4-hydroxynonenal-modified brain proteins in Alzheimer's disease: Role of lipid peroxidation in Alzheimer's disease pathogenesisPROTEOMICS - CLINICAL APPLICATIONS, Issue 6 2009Marzia Perluigi Abstract Numerous studies have shown that neuronal lipids are highly susceptible to oxidative stress including in those brain areas directly involved in the neurodegenerative process of Alzheimer's disease (AD). Lipid peroxidation directly damages membranes and also generates a number of secondary biologically active products (toxic aldehydes)that are capable of easily attacking lipids, proteins, and DNA. Accumulating evidence has demonstrated regionally increased brain lipid peroxidation in patients with AD; however, extensive studies on specific targets of lipid peroxidation-induced damage are still missing. The present study represents a further step in understanding the relationship between oxidative modification of protein and neuronal death associated with AD. We used a proteomics approach to determine specific targets of lipid peroxidation in AD brain, both in hippocampus and inferior parietal lobule, by coupling immunochemical detection of 4-hydroxynonenal-bound proteins with 2-D polyacrylamide gel electrophoresis and MS analysis. We identified 4-hydroxynonenal-bound proteins in the hippocampus and inferior parietal lobule brain regions of subjects with AD. The identified proteins play different biological functions including energy metabolism, antioxidant system, and structural proteins, thus impairing multiple molecular pathways. Our results provide further evidence for the role of lipid peroxidation in the pathogenesis of AD. [source] Candidate antigens specifically detected by cerebrospinal fluid-IgG in oligoclonal IgG bands-positive multiple sclerosis patientsPROTEOMICS - CLINICAL APPLICATIONS, Issue 7 2007Masashi Nakamura Dr. Abstract The aim of the present study was to detect antigenic proteins that react specifically with cerebrospinal fluid (CSF)-IgG from oligoclonal IgG bands (OB)-positive multiple sclerosis (MS) patients. To identify such antigenic proteins, we developed a rat brain proteome map using 2-DE and applied it to the immunoscreening of brain proteins that react with CSF-IgG but not with serum-IgG in OB-positive MS patients. After sequential MALDI-TOF mass spectrometry, eight proteins [two neuronal proteins (tubulin ,-2 and , enolase-2), HSP-1, Tpi-1 protein and cellular enzymes (creatine kinase, phosphopyruvate hydratase, triosephosphate isomerase and phosphoglycerate kinase-1)] were identified as candidate antigens in seven MS patients. Reactivity to tubulin was seen in Western blotting in four patients, and CSF-specific anti-tubulin IgG was detected in one patient. In addition, CSF-specific anti-gamma enolase IgG was found in another patient. These findings suggest that intrathecal immune responses may occur against a broad range of proteins in MS. [source] | |||||||||||||