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)

Microtubule-associated proteins (MAPs) promote tubulin polymerization, whereas colchicine inhibits this process. In this paper, MAPs have been shown to inhibit colchicine binding to tubulin in a competitive manner. Attempts were made to identify which of the MAPs fraction(s) was responsible; both tau protein (a thermostable molecule with a molecular weight of approximately 70,000) and a high molecular weight fraction (HMW) were able to compete with colchicine. In contrast, Mg2+, which also induces microtubule assembly in vitro, had no effect on colchicine binding to tubulin.
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PMID:Competitive inhibition of colchicine binding to tubulin by microtubule-associated proteins. 28 77

The role of microtubule-associated proteins in the assembly of tubulin to microtubules in vitro has been studied. 1. It has been confirmed that pure tubulin obtained by phosphocellulose column chromatography does not significantly assemble in vitro in the absence of minor components which co-polymerize with tubulin. Although tubulin aggregates in a morpholino-ethanesulfonate buffer containing high Mg2+ concentrations, this process was neither inhibited by Ca2+ or colchicine, nor reversed by cold exposure. 2. Microtubule-associated proteins were prepared, either by phosphocellulose column chromatography or by a direct method based on boiling reassembled microtubules in the presence of 2 mM dithiothreitol and 0.75 M NaCl. From each of these preparations two protein fractions were purified, either by Ultrogel ACA34 chromatography or by sucrose gradient ultracentrifugation. The first one, with a high molecular weight, did not promote tubulin assembly; ageing of this material did not induce any activity. On the other hand, the second fraction, with an apparent molecular weight of 70 000 (tau protein), when almost completely purified, was active in promoting assembly. Thus a single specific protein is able to promote assembly of pure tubulin.
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PMID:Microtubule assembly in vitro. Purification of assembly-promoting factors. 91 95

The molecular mechanism of pathological aggregation of microtubule-associated protein tau during neurodegeneration is unclear. In the present study, the in vitro effect of various metal ions on the aggregation of tau was examined using paired helical filament tau (PHF-tau) obtained from corticobasal degeneration (CBD) and Alzheimer's disease (AD) brains as well as normal human tau proteins isolated from fetal and adult brains and a recombinant system. Among the metal ions tested, Ca2+ and Mg2+ effectively induced formation of approximately 340 kD aggregates of PHF-tau but not normal tau proteins as determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and immunoblotting. Al3+ and Fe2+ precipitated both PHF-tau and normal tau protein as SDS-insoluble pellets. The other metal ions examined (Cu2+, Zn2+, and Li+) were inactive and caused neither aggregation nor precipitation of any tau protein. Intermixing experiments using PHF-tau and various normal tau preparations showed that the 340-kD aggregates induced by Ca2+ contained PHF-tau but not normal tau regardless whether unmodified (recombinant) or highly phosphorylated (fetal brain) tau proteins were used. The present results suggest that post-translational modifications other than the fetal-type phosphorylation are required for Ca2+- and Mg2+-dependent aggregation of PHF-tau and that the regional elevation of these ions may trigger pathological deposition of PHF-tau in certain neurodegenerative disorders.
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PMID:Ca2+ and Mg2+ selectively induce aggregates of PHF-tau but not normal human tau. 989 Apr 32

Magnesium (Mg) is a crucial divalent cation with more than 300 cellular functions. This ion shows therapeutic properties in several neurological diseases. Although there are numerous basic evidences showing that Mg can inhibit pathological processes involved in neuroglial degeneration, this low-cost option is not well-considered in clinical research and practice for now. Nevertheless, none of the expensive drugs currently recommended by the classic guidelines (in addition to physiological rehabilitation) had shown exceptional effectiveness. Herein, focusing on Alzheimer's disease (AD), we analyze the therapeutic pathways that support the use of Mg for neurogenesis and neuroprotection. According to experimental findings reviewed, Mg shows interesting abilities to facilitate toxin clearance, reduce neuroinflammation, inhibit the pathologic processing of amyloid protein precursor (APP) as well as the abnormal tau protein phosphorylation, and to reverse the deregulation of N-methyl-D-aspartate receptors. Currently, some crucial details of the mechanisms involved in these proved effects remain elusive and clinical background is poor. Therefore, further studies are required to enable a better overview on pharmacodynamic targets of Mg and thus, to find optimal pharmacologic strategies for clinical use of this ion.
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PMID:Can magnesium reduce central neurodegeneration in Alzheimer's disease? Basic evidences and research needs. 3090 44