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)

Recently several responsible genes for hereditary neurodegenerative disorders were identified. In some of them the gene products were found to be aggregated. In the case of Alzheimer disease beta protein and apolipoprotein E accumulated in senile plaques. In CAG repeat diseases the polyglutamine aggregates in neuronal nuclei. More recently alpha synuclein accumulates in Lewy bodies in Parkinson disease and tau protein accumulates in NFT of hereditary frontotemporal dementia with tau mutation. Those results suggested that the responsible gene products accumulates in the lesion which the products involve in. However, presenilin which is one of the genes for familial Alzheimer disease accumulates in NFT and on the other hand its mutation changes the production ratio of beta 1-42/40, suggesting that the abnormal gene products not simply accumulate the lesion that it involved. The gene products accumulate in different lesions such as in nuclei of polyglutamine diseases, extracellular plaque and cytoplasm of prion disease and extracellular plaques in Alzheimer disease. Some of them are ubiquitinated and some of them are not. Thus the accumulating process in these disorders seems apparently same but is essentially different. We should study more precisely each pathological process of those disorders.
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PMID:[Neuronal cell death--what we can see and what we cannot]. 1037 83

The dementia of the Alzheimer type (DAT) is a chronic neurodegenerative illness. It will continue to increase because of rising life expectancy in the industrialized countries. Apart from the physicians interest to treat, there is also an economically justified interest to reduce the disease progression in this group of patients. The main intention of the treating physicians is to keep their patients independent as long as possible. Up to now Alzheimer's disease can only be treated symptomatically. The verified diagnosis of DAT still depends on the neuropathological investigation of brain tissue. Therefore the clinical diagnosis of DAT during lifetime should be supported by chemical analysis of typical changes in the cerebrospinal fluid (CSF) at an early stage. Meanwhile, several therapeutics with proven effectiveness in clinical studies are certified for the symptomatic treatment of DAT. However, these therapeutics are still relatively expansive. Due to this fact the clinical diagnosis of DAT should be supported by clinical-chemical markers before the beginning of such a treatment. In this paper we present the diagnostic steps in dementia patients, who are examined in our departments. Patients suspicious of DAT always are asked for a spinal tap in addition to other diagnostic tools. In case of a typical clinical constellation, the exclusion of a primarily vascular dementia as well as the proof of decreased A beta 1-42 peptides and an increased tau protein in CSF we recommend the new drugs for DAT as meaningful and justified therapeutics to yield optimal treatment.
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PMID:[Diagnostic steps in Alzheimer dementia before treatment with new antidimentives]. 1092 50

Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N-acetyl-L-cysteine (NAC) on beta-amyloid (A beta) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H(2)O(2), UV light and toxic A beta peptides). A beta and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H(2)O(2), UV light, A beta 1-42 and toxic A beta 25-35, but not the inactive A beta 35-25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre-treated with 30 mM NAC. Cells exposed to H(2)O(2), UV light and A beta 25-35, but not A beta 35-25, secrete significantly higher amounts of A beta 1-40 and A beta 1-42 into the culture medium. NAC pre-treatment increased the release of A beta 1-40 compared with controls and potentiated the release of both A beta 1-40 and A beta 1-42 in A beta 25-35-treated cells. Tau phosphorylation was markedly reduced by H(2)O(2) and UV light but increased by A beta 25-35. NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment.
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PMID:N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation. 1114 96

Recently, it has become important to diagnose Alzheimer's Disease (AD) at an early stage due to the development of AD therapy. Also, there is increasing recognition of a class of elderly people with complaints of memory loss but who nevertheless do not meet the criteria for dementia. "Mild cognitive impairment" (MCI) is the term used for this disorder, and amnestic MCI is highly converted to AD. In this study we evaluated the accuracy of diagnosis of amnestic MCI by cerebrospinal fluid total-tau protein (CSF/total-tau), cerebrospinal fluid amyloid beta 1-42 protein (CSF/A beta 1-42), and cerebral blood flow in the posterior cingulate cortex using SPECT. CSF/total-tau was the most appropriate to discriminate between normal cognitive individuals and those with amnestic MCI. We also evaluated the CSF/total-tau and MRI images between patients with stable MCI and those with progressive MCI, including those who converted to AD in the following two years. The stable type was characterized by normal CSF/total-tau levels and relatively high grade periventricular white matter lesions (PWML). Conversely, the progressive type was characterized by high CSF-tau levels and relatively low grade PWML. We speculate that stable MCI is due to ischemic change with in the white matter lesion, while progressive MCI may represent a previous stage of AD.
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PMID:[Diagnosing the mild cognitive impairment stage of Alzheimer's disease]. 1516 76

Over 40 million people worldwide suffer from dementia. This number is projected to exceed 110 million by 2050 because of the aging of the worldwide population, especially in lower- and middle-income countries. The most common cause of dementia is believed to be Alzheimer's, a brain disease associated with deposition of beta-amyloid protein and hyperphosphorylation of intraneuronal tau protein leading to synaptic degradation, neuronal loss, brain circuit disruption, a range of symptoms, and eventually, if the person lives long enough, death. Over the last few decades, treatment development has focused on the deposition of beta-amyloid protein (A-beta 1-42) that is produced in the brain in huge quantities continuously and is thought to be toxic. Unfortunately, amyloid oriented therapies targeting individuals with dementia, or its prodrome mild cognitive impairment (MCI), have not been successful therapeutically even though they have been associated with reductions in amyloid. Currently, efforts are underway to deliver these therapies to individuals with very early symptoms or at risk for Alzheimer's dementia by virtue of genetics or a brain amyloid PET scan. Results from these studies are expected to begin to emerge by early 2020. In the meantime, since the amyloid hypothesis has been called into question, a number of different avenues are being pursued for treatment development. These are driven in part by new findings related to the polygenic nature of Alzheimer's as well as the interaction between this brain disease with factors such as brain vascular disease, insulin resistance, and/or brain inflammation. The expected future of AD treatment development is thought to be precision medicine.
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PMID:Treatment Development for Alzheimer's Disease: How Are We Doing? 3246 53