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)

The immunolocalization of presenilin in human brain was studied using two antibodies raised against different portions of presenilin 1 (S182) protein. A granular staining was found in the cytoplasm of neurons in cortical layers III and V. One of the antibodies, also reactive to presenilin 2 (E5-1) protein, additionally stained dendrites and axons. This was seen in normal brains as well as in brains affected by Alzheimer's disease. Less prominent immunolabeling was noted in some senile plaques. No relationship to neurofibrillary tangles was found in double-labeling experiments combined with anti-paired helical filament-tau antibody (AT8). The widespread expression of presenilin in normal brain suggests a physiological role of the protein.
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PMID:Widespread immunoreactivity of presenilin in neurons of normal and Alzheimer's disease brains: double-labeling immunohistochemical study. 889 Oct 63

In this paper the actual issues of pathomorphology and pathogenesis of Alzheimer's disease are discussed. The importance of beta-amyloid is recognized. The linkage between late-onset form of Alzheimer's disease and the mutations of gene encoding the amyloid precursor protein (on chromosome 21) was found. Phosphorylation of paired helical filament (which are composed of tau protein) plays the important role. There is evidence for a strong association between apolipoprotein E genotype (on chromosome 19) and late-onset dementia of Alzheimer's type. Two more genes were recently identified: PS-1 and PS-2. Their mutations occur in 70-80% cases of early-onset form of the disease. There is much information about the role of head injury, cholinergic deficiency, estrogen, nerve growth factor and the decline in brain glucose metabolism. Our current knowledge can lead to development of prevention strategies and early recognition of Alzheimer's disease.
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PMID:[Pathomorphology and pathogenesis of changes in Alzheimer's disease]. 992 Sep 95

The serious and growing impact of the neurodegenerative disorder Alzheimer's disease (AD) as an individual and societal burden raises a number of key questions: Can a blanket test for Alzheimer's disease be devised forecasting long-term risk for acquiring this disorder? Can a unified therapy be devised to forestall the development of AD as well as improve the lot of present sufferers? Inflammatory and oxidative stresses are associated with enhanced risk for AD. Can an AD molecular signature be identified in signaling pathways for communication within and among cells during inflammatory and oxidative stress, suggesting possible biomarkers and therapeutic avenues? We postulated a unique molecular signature of dysfunctional activity profiles in AD-relevant signaling pathways in peripheral tissues, based on a gain of function in G-protein-coupled bradykinin B2 receptor (BKB2R) inflammatory stress signaling in skin fibroblasts from AD patients that results in tau protein Ser hyperphosphorylation. Such a signaling profile, routed through both phosphorylation and proteolytic cascades activated by inflammatory and oxidative stresses in highly penetrant familial monogenic forms of AD, could be informative for pathogenesis of the complex multigenic sporadic form of AD. Comparing stimulus-specific cascades of signal transduction revealed a striking diversity of molecular signaling profiles in AD human skin fibroblasts that express endogenous levels of mutant presenilins PS-1 or PS-2 or the Trisomy 21 proteome. AD fibroblasts bearing the PS-1 M146L mutation associated with highly aggressive AD displayed persistent BKB2R signaling plus decreased ERK activation by BK, correctible by gamma-secretase inhibitor Compound E. Lack of these effects in the homologous PS-2 mutant cells indicates specificity of presenilin gamma-secretase catalytic components in BK signaling biology directed toward MAPK activation. Oxidative stress revealed a JNK-dependent survival pathway in normal fibroblasts lost in PS-1 M146L fibroblasts. Complex molecular profiles of signaling dysfunction in the most putatively straightforward human cellular models of AD suggest that risk ascertainment and therapeutic interventions in AD as a whole will likely demand complex solutions.
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PMID:Molecular profiling reveals diversity of stress signal transduction cascades in highly penetrant Alzheimer's disease human skin fibroblasts. 1924 75