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)

Axonal damage is now being recognized as a common finding in multiple sclerosis (MS) lesions and a cause of irreversible neurological damage. Attempts to identify markers of early axonal damage are of great significance. This prompted us to examine the microtubule-associated protein tau in the cerebrospinal fluid (CSF) of patients with MS vs. controls. Tau was measured by double antibody sandwich ELISA. Increased CSF tau levels were found in MS as compared to controls (medians 249.6 and 135 pg/ml respectively, p<0.001). Half of the MS patients presented with levels above the upper limit of the controls. A significant increase vs. controls was found in both relapsing-remitting and progressive subtypes. These data may indicate axonal impairment in a subpopulation of MS patients and may provide a tool for the estimation of axonal damage during life.
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PMID:Increased cerebrospinal fluid tau protein in multiple sclerosis. 1082 54

The examination of biochemical markers of the damage of the central nervous system may be the excellent complement of the neuroimaging methods. There are factors in the cerebrospinal fluid which indicate the damage of the precise structures of the CNS. In this paper there are described the main markers which are used in diagnostic multiple sclerosis: myelin basic protein (MBP) as a marker of demyelination of the white matter, neuron specific enolase (NSE) as a marker of neuronal damage, tau protein, 14-3-3 protein, neurofilament protein-subunit light (NFL) as markers of axonal damage and S-100 protein and glial fibrillary acidic protein as markers of astroglial damage.
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PMID:Biochemical markers of damage of the central nervous system in multiple sclerosis. 1197 45

The recent re-discovery of axonal damage in multiple sclerosis has led to a renewed interest in neurodegenerative mechanisms of the disease. Transected or injured axons release several molecules from their proximal extremity into the intercellular space. Although these molecules can be measured, however, a biological marker of axonal and neuronal degeneration is still lacking. Cytoskeleton structural proteins like actin, tubulin, L-neurofilaments and tau protein, axon-specific antibodies, other neuronal or glial proteins like S-100, 14-3-3 and glial fibrillary acid protein, neuronal specific enolase, and nitric oxide and its metabolites are some of the putative markers that deserve further investigation and validation. At present, none of them fulfils the criteria of applicability in clinical practice, and the levels of N-acetylaspartate determined by magnetic resonance spectroscopy remain the most reliable measure of axonal damage.
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PMID:Biological indicators of the neurodegenerative phase of multiple sclerosis. 1465 89

Recently it has been shown that axonal damage occurs in all stages of multiple sclerosis (MS) and can be detected very early in the course of the disease. Axonal pathology has been related to the inflammatory demyelinating environment, but its dependence on inflammation is still unknown. We measured tau protein and 14-3-3, two intracellular proteins expressed in neurons and glial cells, in the cerebrospinal fluid (CSF) of 114 patients with MS, in 79 patients with other inflammatory neurological diseases (IND) and in the CSF of 60 patients with non-inflammatory neurological diseases (NIND) as controls. Concentrations of tau protein and 14-3-3 were measured by enzymelinked immunoassay and were correlated to the following immune parameters in the CSF: leukocyte cell count, total protein, albumin CSF/serum ratio as a marker of disruption of the blood-brain barrier, immunoglobulin (IgG concentrations and IgG index as an indicator for intrathecal synthesis of IgG in the CSF). Both in MS and IND tau protein levels were significantly higher than in NIND (p<0.05). In MS patients levels of tau protein were positively correlated with the IgG index (p<0.05) and this association was present in both relapsing remitting MS (RRMS) (p<0.05) and progressive MS (p<0.05). Tau and 14-3-3 were also correlated with the IgG index in patients with IND (p<0.05). These findings strengthen the hypothesis that inflammation may be at least in part responsible for the axonal damage observed in MS patients.
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PMID:Tau protein and 14-3-3 are elevated in the cerebrospinal fluid of patients with multiple sclerosis and correlate with intrathecal synthesis of IgG. 1508 85

Axonal damage is a major morphological correlate and cause of permanent neurological deficits in patients with multiple sclerosis (MS), a multifocal, inflammatory and demyelinating disease of the central nervous system. Hyperphosphorylation and pathological aggregation of microtubule-associated protein tau is a common feature of many neurodegenerative diseases with axonal degeneration including Alzheimer's disease. We have therefore analyzed tau phosphorylation, solubility and distribution in the brainstem of rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Tau was hyperphosphorylated at several sites also phosphorylated in Alzheimer's disease and became partially detergent-insoluble in EAE brains. Morphological examination demonstrated accumulation of amorphous deposits of abnormally phosphorylated tau in the cell body and axons of neurons within demyelinating plaques. Hyperphosphorylation of tau was accompanied by up-regulation of p25, an activator of cyclin-dependent kinase 5. Phosphorylation of tau, activation of cdk5, and axonal pathology were significantly reduced when diseased rats were treated with prednisolone, a standard therapy of acute relapses in MS. Hyperphosphorylation of tau was not observed in a genetic or nutritional model of axonal degeneration or demyelination, suggesting that inflammation as detected in the brains of rats with EAE is the specific trigger of tau pathology. In summary, our data provide evidence that axonal damage in EAE and possibly MS is linked to tau pathology.
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PMID:Hyperphosphorylation and aggregation of tau in experimental autoimmune encephalomyelitis. 1549 5

Tau2 antibody recognizes a phosphorylation-independent epitope that is pathologically modified as tau protein is phosphorylated to form neurofibrillary tangles of Alzheimer's disease (AD). Similar modification of tau2 epitope can be induced even in the absence phosphorylation of tau, as we first demonstrated in ischemic foci and in glial cytoplasmic inclusions (GCIs) of multiple system atrophy. This modification of tau2 epitope is distinguishable from those observed in degenerative tauopathies because (1) it is a conformational change, which is reversible upon exposure to a detergent; (2) it shows an absence of fibrils composed of phosphorylated tau protein; and (3) it is characterized by the lack of immunohistochemical labeling by anti-tau antibodies other than tau2. In this study, we expanded this observation to inflammatory foci of different pathologies (human immunodeficiency virus encephalopathy, progressive multifocal leukoencephalopathy or multiple sclerosis) by examining formalin-fixed, paraffin-embedded sections immunostained with a panel of anti-tau antibodies. It was found that tau2 was the only anti-tau antibody that immunolabeled microglia/macrophages in these lesions, and this immunoreactivity was reversibly diminished upon exposure to a detergent. Exclusive apparition of tau2 immunoreactivity in these cells without neurofibrillary pathology may be a secondary event shared with ischemic foci and GCIs. It is, however, related to a unique conformational state of tau, possibly grouped under the name of "tautwopathy", that may represent an initial stage of tau deposition distinct from degenerative tauopathies characterized by fibrils composed of phosphorylated tau protein.
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PMID:Exclusive induction of tau2 epitope in microglia/macrophages in inflammatory lesions-tautwopathy distinct from degenerative tauopathies. 1554 33

Total-tau protein is considered the marker of axon damage whereas the abnormally phosphorylated tau forms are mainly associated with Alzheimer's disease. An increase in total-tau levels was observed in neurodegenerative diseases, including multiple sclerosis (MS). In order to find out whether the phosphorylated tau forms occur in MS patients and to evaluate their clinical significance, the levels of total-tau (t-tau) and tau phosphorylated at Thr 181 (p-tau) were determined in 60 MS patients (40 during relapse including 18 with the first relapse and 20 stable) and in 18 age-matched controls. The determinations were conducted in the cerebrospinal fluid (CSF) using the ELISA method. The levels of t-tau and p-tau were higher in MS patients than in controls; however, increased levels were not related to the clinical activity of the disease. In CSF of the patients with the first relapse the level of t-tau was significantly increased whilst the level of p-tau was not elevated.
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PMID:The CSF levels of total-tau and phosphotau in patients with relapsing-remitting multiple sclerosis. 1599 19

Axonal injury and glial activation are an early neuropathologic event in adults with multiple sclerosis. To investigate whether markers of axonal injury and glial activation are already elevated in the cerebrospinal fluid of children with multiple sclerosis, we studied the cerebrospinal fluid of 25 children with multiple sclerosis and 67 controls for the presence of tau, phospho-tau, and S-100B proteins using specific enzyme-linked immunoabsorbent assays. In general, tau, phospho-tau, and S-100B protein levels did not differ significantly between groups. However, in a subgroup of nine children with multiple sclerosis, all of whom had prominent clinical symptoms at the time of lumbar puncture and radiologic disease activity, tau protein levels were significantly elevated when compared with other controls. These data indicate that axonal injury is not restricted to adult multiple sclerosis but can already occur in children with multiple sclerosis.
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PMID:Tau, phospho-tau, and S-100B in the cerebrospinal fluid of children with multiple sclerosis. 1641 78

Although the diagnosis of multiple sclerosis (MS) may be clinically suspect and the magnetic resonance imaging findings compatible, cerebrospinal fluid (CSF) analysis remains mandatory in order to support the diagnosis. This is especially important since our understanding of the defining disease pathogenesis remains incomplete. However, there is no specifically diagnostic CSF test. And until recently, laboratory techniques for CSF analysis had not been rigorously standardized. Unconcentrated CSF without fixative should be used for the determinations of cell count and differential, protein and glucose, lactate, myelin basic protein, and the CSF/serum albumin ratio which is an indicator of blood-CSF barrier disruption. Additionally, CSF immunoglobulin-gamma (IgG) determinations are of major importance and are now included in the MS diagnostic criteria. Testing for oligoclonal IgG bands utilizing isoelectric focusing with IgG immunoblotting, the IgG synthesis rate, and the IgG index should be included. CSF analysis for kappa light chains and IGM may be diagnostically helpful. The search for biomarkers including those possibly present in the CSF which could predict and assess the course as well as response to treatment in a particular MS patient has not yet been successful. CSF immunoglobulin and T-cell/B-cell patterns, soluble HLA class I and II antigens, nitrous oxide metabolites, neurofilament and microtubule components and antibodies, tau protein, 14-3-3-protein, neuronal cell and intercellular adhesion molecules, and chemokines are actively being investigated as MS biomarkers.
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PMID:Cerebrospinal fluid analysis in multiple sclerosis. 1753 49

Unlike other neuroinflammatory disorders, like Parkinson's disease, Huntington's disease and multiple sclerosis, little is still known of the role of the endocannabinoid system in Alzheimer's disease (AD). This is partly due to the poor availability of animal models that are really relevant to the human disease, and to the complexity of AD as compared to other neurological states. Nevertheless, the available data indicate that endocannabinoids are likely to play in this disorder a role similar to that suggested in other neurodegenerative diseases, that is, to represent an endogenous adaptive response aimed at counteracting both the neurochemical and inflammatory consequences of beta-amyloid-induced tau protein hyperactivity, possibly the most important underlying cause of AD. Furthermore, plant and synthetic cannabinoids, and particularly the non-psychotropic cannabidiol, might also exert other, non-cannabinoid receptor-mediated protective effects, including, but not limited to, anti-oxidant actions. There is evidence, from in vivo studies on beta-amyloid-induced neurotoxicity, also for a possible causative role of endocannabinoids in the impairment in memory retention, which is typical of AD. This might open the way to the use of cannabinoid receptor antagonists as therapeutic drugs for the treatment of cognitive deficits in the more advanced phases of this disorder. The scant, but nevertheless important literature on the regulation and role of the endocannabinoid system in AD, and on the potential treatment of this disorder with cannabinoids and endocannabinoid-based drugs, are discussed in this mini-review.
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PMID:The role of the endocannabinoid system in Alzheimer's disease: facts and hypotheses. 1878 80


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