Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We introduce a new procedure to study kinase substrates in postmortem human brain. By adding purified exogenous protein kinase C (PKC) and the phospholipid phosphatidylserine to brain homogenates in vitro we are able to analyze PKC substrates. A human 53-kDa phosphoprotein is described that appears to be homologous to rat and monkey protein F1 (GAP-43). This identity is based on molecular weight, isoelectric point, phosphorylation by exogenous protein kinase C, enhancement of its phosphorylation by three activators (phospholipids, calcium and phorbol esters), phosphopeptide maps, and cross-reactivity with an antibody raised against rat protein F1. Protein F1 is a PKC substrate associated with synaptic plasticity and nerve growth. Its phosphorylation in rat brain has been correlated with long-term potentiation, an electrophysiological model of memory. In the present study of normal brain, human protein F1 shows an occipitotemporal in vitro phosphorylation gradient. This is consistent with previous observations in nonhuman primates. This gradient is less pronounced in Alzheimer's disease (AD). Changes in the in vitro phosphorylation pattern of three other non-PKC substrates in Alzheimer's disease, including one with characteristics similar to microtubule-associated protein tau, are also reported. These results suggest that protein phosphorylation can be studied in postmortem human brain and that PKC-mediated phosphorylation of protein F1, already linked to synaptic plasticity and memory, may be altered in AD.
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PMID:Contrasting patterns of protein phosphorylation in human normal and Alzheimer brain: focus on protein kinase C and protein F1/GAP-43. 182 25

In view of existing drugs (acetylcholine esterase inhibitors) and emerging therapeutic compounds (e.g. neuroprotective and anti-inflammatory compounds), CSF markers would be of great use to improve the clinical diagnostic accuracy of Alzheimer's disease (AD). Correct identification of AD would be especially important early in the course of the disease, when the clinical diagnosis is difficult, and drugs have the greatest potential of being effective. Biochemical markers for AD include ApoE genotyping, where the ApoE epsilon 4 allele has proven to have a high predictive value for AD. Biochemical markers for AD also include several potential cerebrospinal fluid (CSF) markers: beta-amyloid(1-42), possibly reflecting amyloid deposition and formation of senile plaques; PHFtau protein a marker for the phosphorylation state of tau, and formation of neurofibrillary tangles; (total)tau protein, a normal axonal protein, as a marker for ongoing neuronal and axonal degeneration; synaptic vesicle proteins, e.g. synaptotagmin, a synaptic vesicle protein which is found in the CSF, as markers for synaptic activity or degeneration; neuromodulin or growth-associated protein GAP-43, as a marker for synaptic degeneration, and the CSF/serum albumin ratio, as a marker for blood-brain barrier damage, used to exclude patients with concomitant cerebrovascular pathology. However, although CSF markers may identify different pathogenic processes in AD, there is no such process that is specific for AD, and thus little hope of ever finding a single CSF biochemical marker that gives an absolute discrimination between AD and other dementia disorders. Instead, combination of several CSF biochemical markers, each reflecting a pathogenic process, may increase both the sensitivity and specificity. Further, the accuracy of the clinical diagnosis of AD may increase if the diagnosis is based on the summarised information gained from the clinical examination, brain-imaging techniques (SPECT, CT/MRT scans), and biochemical markers. Using this approach, CSF markers have a large potential to help to differentiate AD from the most problematic differential diagnoses, especially age-associated memory impairment, depressive pseudo-dementia, Parkinson's disease, and frontal lobe dementia.
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PMID:Combination of the different biological markers for increasing specificity of in vivo Alzheimer's testing. 970 Jun 60

Amyloid-beta (A beta) is the main component of senile plaques, one of the hallmarks of Alzheimer's disease. Our results showed that A beta(25-35) decreased neuronal viability while it increased generation of reactive oxygen species (ROS). Under these circumstances, albumin (BSA) prevented ROS production and neuronal death in a dose- and time-dependent manner. In addition, BSA partially prevented the decrease in the expression of GAP-43, MAP-2, and tubulin, and the phosphorylation of tau protein caused by A beta, suggesting that BSA protects against the loss of plasticity caused by the peptide. Our findings suggest that BSA exerts its protective effect by binding to A beta in an equimolecular way, which prevents heterodimer (A beta-BSA) entry into neurons. In fact, BSA prevented A beta internalization, as shown by confocal immunocytochemistry, suggesting that BSA causes its protective effect by sequestrating A beta, which cannot reach its intracellular targets. This is consistent with the idea that A beta must enter neurons to exert its deleterious effects.
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PMID:Albumin-blunted deleterious effect of amyloid-beta by preventing the internalization of the peptide into neurons. 1954 22

Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, but procedures as computerized tomography (CT) may deliver a significant radiation dose to the patient. Recently, awareness has been raised about possible non-cancer consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. In the present study neonatal NMRI mice were whole body irradiated with a single dose of gamma radiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of both sexes were observed for spontaneous behaviour in a novel home environment. The neuroproteins CaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus were analysed 24h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10. A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old mice was observed, where both males and females displayed a modified habituation, indicating reduced cognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male mice showed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined critical period of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, an elevation of tau protein was observed in male mice displaying reduced cognitive function.
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PMID:Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice. 2526 67