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Dysregulation of dynorphins in Alzheimer disease
Department of Clinical Neuroscience, Karolinska Institute and Hospital, Stockholm, Sweden. (Molecular neuropsychopharmacology)
Department of Clinical Neuroscience, Karolinska Institute and Hospital, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institute and Hospital, Stockholm, Sweden. (Molecular neuropsychopharmacology)
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Que., Canada.
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2007 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 28, no 11, 1700-8 p.Article in journal (Refereed) Published
Abstract [en]

The opioid peptides dynorphins may be involved in pathogenesis of Alzheimer disease (AD) by inducing neurodegeneration or cognitive impairment. To test this hypothesis, the dynorphin system was analyzed in postmortem samples from AD and control subjects, and subjects with Parkinson or cerebro-vascular diseases for comparison. Dynorphin A, dynorphin B and related neuropeptide nociceptin were determined in the Brodmann area 7 by radioimmunoassay. The precursor protein prodynorphin, processing convertase PC2 and the neuroendocrine pro7B2 and 7B2 proteins required for PC2 maturation were analyzed by Western blot. AD subjects displayed robustly elevated levels of dynorphin A and no differences in dynorphin B and nociceptin compared to controls. Subjects with Parkinson or cerebro-vascular diseases did not differ from controls with respect to any of the three peptides. PC2 levels were also increased, whereas, those of prodynorphin and pro7B2/7B2 were not changed in AD. Dynorphin A levels correlated with the neuritic plaque density. These results along with the known non-opioid ability of dynorphin A to induce neurodegeneration suggest a role for this neuropeptide in AD neuropathology.

Place, publisher, year, edition, pages
2007. Vol. 28, no 11, 1700-8 p.
Keyword [en]
Dynorphin, Alzheimer disease, Neurodegeneration, Excitotoxicity, Pro-hormone convertase 2, 7B2, Prodynorphin, Cognition
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-120089DOI: 10.1016/j.neurobiolaging.2006.07.002PubMedID: 16914231OAI: oai:DiVA.org:uu-120089DiVA: diva2:302462
Available from: 2010-03-08 Created: 2010-03-07 Last updated: 2011-04-26Bibliographically approved

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Yakovleva, TatjanaKuzmin, A.Bakalkin, G.

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