PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9263191

Decrease in adenylate cyclase activity antecedes neurofibrillary tangle formation.

T G Ohm·M Schmitt·J Bohl·B Lemmer
View original source ↗Export metadata ↓

Abstract

In previous studies, the formation of cAMP was seen to be significantly reduced in various brain regions in Alzheimer patients. Recently, a staging system was introduced in which Alzheimer-related. histopathological changes were classified according to the pattern of alterations rather than their density. In this study, we examined the degree of correlation between these stages and the postmortem activity of the CAMP-generating enzyme adenylate cyclase. Our findings suggest that forskolin-stimulated adenylate cyclase activity is significantly decreased before major neurofibrillary changes develop. Early impairment of postreceptor signalling could have potentially important consequences for drug treatment and/or for the development of neurofibrillary changes.

Explore related subjects

Adenylyl CyclasesAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedNeurofibrillary TanglesPostmortem ChangesTime FactorsJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

T G Ohm, M Schmitt, J Bohl, B Lemmer. Decrease in adenylate cyclase activity antecedes neurofibrillary tangle formation.. https://doi.org/10.1016/s0197-4580(97)80307-7

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2004

Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse.

Rapid expansion of available data, both phenotypic and genotypic, for multiple strains of mice has enabled the development of new methods to interrogate the mouse genome for functional genetic perturbations. In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purpose of dissecting genetic traits. In mouse, the current single nucleotide polymorphism (SNP) data have lacked the density across the genome and coverage of enough strains to properly achieve this goal. To remedy this, 470,407 allele calls were produced for 10,990 evenly spaced SNP loci across 48 inbred mouse strains. Use of the SNP set with statistical models that considered unique patterns within blocks of three SNPs as an inferred haplotype could successfully map known single gene traits and a cloned quantitative trait gene. Application of this method to high-density lipoprotein and gallstone phenotypes reproduced previously characterized quantitative trait loci (QTL). The inferred haplotype data also facilitates the refinement of QTL regions such that candidate genes can be more easily identified and characterized as shown for adenylate cyclase 7.

Adenylyl Cyclases↗
PubMed1999

Multiple developmental roles for CRAC, a cytosolic regulator of adenylyl cyclase.

Receptor-mediated activation of adenylyl cyclase (ACA) in Dictyostelium requires CRAC protein. Upon translocation to the membrane, this pleckstrin homology (PH) domain protein stimulates ACA and thereby mediates developmental aggregation. CRAC may also have roles later in development since CRAC-null cells can respond to chemotactic signals and participate in developmental aggregation when admixed with wild-type cells, but they do not complete development within such chimeras. To test whether the role of CRAC in postaggregative development is related to the activation of ACA, chemotactic aggregation was bypassed in CRAC-null cells by activating the cAMP-dependent protein kinase (PKA). While such strains formed mounds, they did not complete fruiting body morphogenesis or form spores. Expression of CRAC in the prespore cells of these strains rescued sporulation and fruiting body formation. This later function of CRAC does not appear to require its PH domain since the C-terminal portion of the protein (CRAC-DeltaPH) can substitute for full-length CRAC in promoting spore cell formation and morphogenesis. No detectable ACA activation was observed in any of the CRAC-null strains rescued by PKA activation and expression of CRAC-DeltaPH. Finally, we found that the development of CRAC-null ACA-null double mutants could be rescued by the activation of PKA together with the expression of CRAC-DeltaPH. Thus, there appears to be a required function for CRAC in postaggregative development that is independent of its previously described function in the ACA activation pathway.

Adenylyl Cyclases↗