Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    German Medical Science; Düsseldorf, Köln
    In:  Hypertonie 2003; 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga; 20031126-20031129; Bonn; DOC03hochV50 /20041111/
    Publication Date: 2004-11-12
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Advanced glycation endproducts ; AGE ; Alzheimer-Erkrankung ; Ätiologie ; Biochemische Hypothesen ; Key words Advanced glycation endproducts ; AGE ; Alzheimer's disease ; Biochemical hypotheses ; Etiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Despite intense efforts, it has not yet been possible to clarify the etiopathogenesis of Alzheimer's dementia. There are, however, hypotheses which focus on certain aspects of this type of dementia, characterized by particular neuropathological alterations and clinical correlates. Recently, evidence has accumulated that advanced glycation endproducts (AGEs) could play an important role in the etiology of the Alzheimer's syndrome. AGEs are generated by an irreversible reaction through the non-enzymatic, long-term glycosylation of proteins. They are strongly resistent to proteolytic processes and induce protein crosslinking. They could thus inhibit the physiological functions of many proteins. Moreover, it is suggested that they contribute to the transformation of the soluble form of β-amyloid into its unsoluble version. AGEs are also demonstrable in neurofibrillary tangles (NFTs). A further mechanism by which AGEs might be pathogenic is via their induction of oxidative stress. AGEs probably exert their pathological effects not only directly because of their chemical properties, but also by indirect receptor-mediated mechanisms. Further investigation of AGE-mediated mechanisms should reveal their role in the etiopathogenesis of the Alzheimer's syndrome and, finally, lead to the development of new pharmacological strategies aimed at inhibiting protein cross-linking.
    Notes: Zusammenfassung Trotz intensiver Bemühungen ist es bislang nicht gelungen, die Ätiopathogenese des Alzheimer-Syndroms endgültig aufzuklären. Es existieren Hypothesen, die zumindest Teilaspekte dieser mit charakteristischen neuropathologischen Veränderungen und typischer klinischer Symptomatik einhergehenden Demenzerkrankung erklären können. In jüngster Zeit häufen sich Hinweise darauf, daß AGE (advanced glycation endproducts) in der Krankheitsentstehung des Alzheimer-Syndroms eine wichtige Rolle spielen könnten. AGE entstehen in einer irreversiblen Reaktion durch nicht-enzymatische, über einen längeren Zeitraum verlaufende Glykosylierung von Proteinen. Sie sind sehr resistent gegenüber proteolytischen Prozessen und induzieren Proteinvernetzungen (crosslinking). Dadurch können sie die physiologische Funktion vieler Proteine hemmen. Darüber hinaus wird vermutet, daß sie zur Umwandlung der löslichen Form des β-Amyloids in die unlösliche Form beitragen können. Auch in den neurofibrillären Tangles (NFT) konnten AGE nachgewiesen werden. Ein weiterer Pathomechanismus der AGE könnte in der Induktion von oxidativem Streß bestehen. Pathologische Effekte üben die AGE vermutlich nicht nur direkt aufgrund ihrer chemischen Eigenschaften aus, sondern auch über indirekte rezeptorvermittelte Mechanismen. Eine verstärkte Erforschung der Bedeutung von AGE in der Ätiopathogenese des Alzheimer-Syndroms könnte auch zur Entwicklung neuer pharmakotherapeutischer Strategien beitragen.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    FEBS Letters 286 (1991), S. 125-128 
    ISSN: 0014-5793
    Keywords: Site-directed mutagenesis ; Steady-state kinetics ; Structure-function
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 25 (1984), S. 0 
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract The mycotoxin aphidicolin, a potent inhibitor of eukaryotic α-type DNA polymerases, interferes with cell division of halobacteria. Drug-treated cells do not divide but elongate considerably. From analyses of macromolecular syntheses in aphidicolin-treated halobacteria we conclude that the primary target of this drug is DNA synthesis, possibly a DNA polymerase. This implies an evolutionary relationship to eukaryotic DNA replication.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1435-1463
    Keywords: Keywords: Advanced glycation endproducts ; Alzheimer's disease ; cytotoxicity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Non-enzymatic glycation of proteins with reducing sugars and subsequent transition metal catalysed oxidations leads to the formation of protein bound "advanced glycation endproducts" (AGEs). They accumulate on long-lived proteins and are for example structural components of the β-amyloid plaques in Alzheimer's disease. Since the oxidation of glycated proteins as well as the interaction of AGEs with cell surface receptors produces superoxide radicals, it was tested in BHK 21 hamster fibroblast cells and SH-SY5Y human neuroblastoma cells if AGEs can exert cytotoxic effects on cells. Cell viability was assessed with three independent tests: MTT – assay (activity of the mitochondrial respiratory chain), lactate dehydrogenase assay (release of cytoplasmatic enzymes, membrane integrity) and Neutral Red assay (active uptake of a hydrophilic dye). Two model AGEs, chicken egg albumin-AGE and BSA-AGE, both caused significant cell death in a dose-dependent manner. The cytotoxic effects of AGEs could be attenuated by α-ketoglutarate and pyruvate, by antioxidants such as thioctic acid and N-acetylcysteine, and by aminoguanidine, an inhibitor of nitric oxide synthase. This suggests that reactive oxygen species as well as reactive nitrogen species contribute to AGE mediated cytotoxicity. Since AGEs accumulate on β-amyloid plaques in AD over time, they may additionally contribute to oxidative stress, cell damage, functional loss and even neuronal cell death in the Alzheimer's disease brain.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1435-1463
    Keywords: Keywords: Oxidative stress ; diabetes ; aging ; advanced glycation endproducts ; lipid peroxidation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Many approaches have been undertaken to understand Alzheimer's disease (AD) but the heterogeneity of the etiologic factors makes it difficult to define the clincally most important factor determining the onset and progression of the disease. However, there is increasing evidence that the previously so-called "secondary factors" such as a disturbed glucose metabolism, oxidative stress and formation of "advanced glycation endproducts" (AGEs) and their interaction in a vicious cycle are also important for the onset and progression of AD. AGEs are protein modifications that contribute to the formation of the histopathological and biochemical hallmarks of AD: amyloid plaques, neurofibrillary tangles and activated microglia. Oxidative modifications are formed by a complex cascade of dehydration, oxidation and cyclisation reactions, subsequent to a non-enzymatic reaction of sugars with amino groups of proteins. Accumulation of AGE-crosslinked proteins throughout life is a general phenomenon of ageing. However, AGEs are more than just markers of ageing since they can also exert adverse biologic effects on tissues and cells, including the activation of intracellular signal transduction pathways, leading to the upregulation of cytokine and free radical production (oxidative stress). Oxidative stress is involved in various divergent events leading to cell damage, including an increase in membrane rigidity, DNA strand breaks and an impairment in glucose uptake. In addition, other age-related metabolic changes such as depletion of antioxidants or decreased energy production by a disturbed glucose metabolism diminish the ability of the cell to cope with the effects of radical-induced membrane, protein and DNA damage. With our improving understanding of the molecular basis for the clinical symptoms of dementia, it is hoped that the elucidation of the etiologic causes, particularly the positive feedback loops involving radical damage and a reduced glucose metabolism, will help to develop novel "neuroprotective" treatment strategies able to interrupt this vicious cycle of oxidative stress and energy shortage in AD.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1435-1463
    Keywords: Maillard reaction ; advanced glycosylation ; tenilsetam ; dementia of Alzheimer type ; amyloid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-enzymatic glycosylation of proteins, also called Maillard reaction, which occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation endproducts (AGEs). Tenilsetam (®CAS 997: (±)-3-(2-thienyl)-2-piperazinone), a cognition-enhancing drug successfully used for treatment of patients suffering from Alzheimer's disease, when included in the Maillard reaction apparently inhibits protein crosslinking by AGEs in vitro. According to the mechanism proposed, Tenilsetam acts via covalent attachment to glycated proteins, thus blocking the reactive sites for further polymerisation reactions. A beneficial effect of Tenilsetam in Alzheimer's disease could come from the interference with AGE-derived crosslinking of amyloid plaques and a decreased inflammatory response by diminished activation of phagocytosing microglia.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...