Showing papers by "Michel Goedert published in 1989"

Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain.

Abstract: We have isolated cDNA clones encoding a 383-amino acid isoform of the human microtubule-associated protein tau. It differs from previously determined tau sequences by the presence of an additional repeat of 31 amino acids, giving four, rather than three, tandem repeats in its carboxy-terminal half. The extra repeat is encoded by a separate exon. Probes derived from cDNA clones encoding the three (type I) and four repeat (type II) tau protein isoforms detected mRNAs for both forms in all adult human brain areas examined. However, in foetal brain only type I mRNA was found. Type I and type II mRNAs were present in pyramidal cells in cerebral cortex. In the hippocampal formation, type I mRNA was found in pyramidal and granule cells; type II mRNA was detected in most, though not all, pyramidal cells but not in granule cells. These observations indicate that tau protein mRNAs are expressed in a stage- and cell-specific manner. Tau protein is found in the protease-resistant core of the paired helical filament, the major constituent of the neurofibrillary tangle in Alzheimer's disease. Taken in conjunction with previous findings, the present results indicate that both the three and four repeat-containing tau protein isoforms are present in the core of the paired helical filament.

Nerve growth factor mRNA and protein increase in hypothalamus in a mouse model of aggression.

Abstract: The effects of intermale aggressive behavior induced by social isolation on the level of nerve growth factor (NGF) mRNA and protein were investigated in central and peripheral mouse tissues. A large increase in NGF mRNA and protein was observed in hypothalamus, with no changes in cerebral cortex, hippocampus, and cerebellum. No change in NGF mRNA levels was found in heart, spleen, vas deferens, and submaxillary salivary gland. The cellular localization of NGF mRNA in the central nervous system was investigated by in situ hybridization. Numerous nerve cells were specifically labeled in preoptic and ventrolateral nuclei of the hypothalamus, as well as in the cornu ammonis region of the hippocampus and throughout all layers of the cerebral cortex, with the highest concentration in layer III. The present results firmly establish that nerve cells constitute the major source in NGF in the brain. They also open the way to understanding the regulation of NGF biosynthesis in the central nervous system.

The repeat region of microtubule-associated protein tau forms part of the core of the paired helical filament of Alzheimer's disease.

Abstract: The paired helical filament, the principal component of the neurofibrillary tangles characteristic of Alzheimer's disease, is shown to consist of two structurally distinct parts. An external fuzzy region can be removed by pronase treatment to leave a pronase-resistant morphologically recognizable core. A monoclonal antibody has been raised which both decorates the core and labels peptide fragments extracted from the core. Amino acid sequence derived from such peptides was used to design oligonucleotide probes with which cDNA libraries were screened and clones coding for the corresponding proteins were isolated. The sequences proved to code for two isoforms of human microtu-bule-associated protein tau, which contained respectively three or four tandem repeats of 31 or 32 amino acids each with a characteristic Pro-Gly-Gly-Gly motif. The patterns of mRNA expression for the two isoforms were found to be stage and cell-type specific but were apparently unaltered in Alzheimer's disease. The repeat region of tau...

Radioligand-binding assays for study of neurotensin receptors.

Abstract: Publisher Summary This chapter discusses the radioligand-binding assays for the study of neurotensin receptors Radioligand-binding studies have provided valuable information concerning the characteristics, the structure–activity relationships, and the cellular localization of neurotensin receptors However, radioligand-binding studies are by their very nature indirect, deducing the existence of a receptor from the characteristics of membrane sites identified through radioligand binding Therefore, the elucidation of the primary structure of neurotensin receptors constitutes the next important step X laevis oocytes injected with brain poly(A) + RNA exhibit an electrophysiological response to neurotensin This, in conjunction with a general technique for cloning neurotransmitter receptors without prior purification and partial amino acid sequence determination, should permit the molecular cloning and sequencing of neurotensin receptors in the near future

Peptide antagonists for use in cancer therapy, and the use of mas oncogene and its product

Abstract: It has been demonstrated that the mas oncogene encodes an angiotensin receptor. A substance which blocks the biological activity of angiotensin may thus be used in the treatment or prevention of tumour development or ectopic hormone production. Suitable substances include angiotensin antagonists, partial agonists to angiotensins, and antibodies to angiotensins. The use of the product of the mas oncogene in an assay system for angiotensin-blocking activity is also claimed.

Utilisation d'antagonistes de peptides dans le traitement du cancer et utilisation de l'oncogene mas et de ses produits

Abstract: Il a ete demontre que l'oncogene mas code pour un recepteur angiotensine. On peut donc utiliser une substance qui arrete l'activite biologique de l'angiotensine dans le traitement ou la prevention de l'evolution des tumeurs ou la production d'hormones ectopiques. Parmi les substances qui conviennent a cela, on compte des antagoniste d'angiotensine, des agonistes partiels des angiotensines et des anticorps aux angiotensines. On decrit egalement l'utilisation du produit de l'oncogene mas dans un systeme d'analyse pour inhiber activite de l'angiotensine.