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

Exposure of rat hippocampal neurons to the peptide amyloid beta (A beta) (25-35) as well as A beta (1-40) peptides enhances phosphorylation of tau to a paired helical filament (PHF)-state through activation of tau protein kinase I (TPK I)/glycogen synthase kinase-3 beta (GSK-3 beta) [Busciglio, J., Lorenzo, A., Yeh, J. and Yankner, B.A., Neuron, 14 (1995) 879-888; Takashima, A., Ishiguro, K., Noguchi, K., Michel, G., Hoshi, M., Sato, K., Takahashi, M., Hoshino, T., Uchida, T. and Imahori, K., Neurosci. Meeting Abstr., 671 (1995) 17]. In order to examine the effects of A beta treatment on intracellular signaling mechanism, we have investigated the role of phosphatidyl inositol-3 (PI-3) kinase in the phosphorylation of tau. A beta (25-35) exposure induced an inactivation of PI-3 kinase and an activation of TPK I/GSK-3 beta in rat hippocampal culture. Wortmannin, an inhibitor of PI-3 kinase, also activated TPK I/GSK-3 beta, leading to an enhancement of tau phosphorylation and neuronal death in hippocampal culture. These results suggest that A beta (25-35) inhibition of PI-3 kinase results in the activation of TPK I/GSK-3 beta, the phosphorylation of tau, and resultant neuronal death in rat hippocampal neurons.
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PMID:Exposure of rat hippocampal neurons to amyloid beta peptide (25-35) induces the inactivation of phosphatidyl inositol-3 kinase and the activation of tau protein kinase I/glycogen synthase kinase-3 beta. 874 40

Cholinergic interneurons, which provide the main source of acetylcholine (ACh) in the striatum, control the striatal local circuits and deeply involve in the pathogenesis of neurodegenerative diseases. Glycogen synthase kinase-3 (GSK-3) is a crucial kinase with diverse fundamental functions and accepted that deregulation of GSK-3 activity also plays important roles in diverse neurodegenerative diseases. However, up to now, there is no direct proof indicating whether GSK-3 activation is responsible for cholinergic dysfunction. In the present study, with combined intracerebroventricular injection of Wortmannin and GF-109203X, we activated GSK-3 and demonstrated the increased phosphorylation level of microtubule-associated protein tau and neurofilaments (NFs) in the rat striatum. The activated GSK-3 consequently decreased ACh level in the striatum as a result of the reduction of choline acetyltransferase (ChAT) activity. The alteration of ChAT activity was due to impaired ChAT distribution rather than its expression. Furthermore, we proved that cellular ChAT distribution was dependent on low phosphorylation level of NFs. Nevertheless, the cholinergic dysfunction in the striatum failed to induce significant neuronal number reduction. In summary, our data demonstrates the link between GSK-3 activation and cholinergic dysfunction in the striatum and provided beneficial evidence for the pathogenesis study of relevant neurodegenerative diseases.
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PMID:Glycogen synthase kinase-3 reduces acetylcholine level in striatum via disturbing cellular distribution of choline acetyltransferase in cholinergic interneurons in rats. 2412 Nov 30