Role of protein kinase B in Alzheimer's neurofibrillary pathology
| Autor: | Sabiha Khatoon, Inge Grundke-Iqbal, Maria Nordlinder, Jin-Jing Pei, Khalid Iqbal, Masatoshi Takeda, Richard F. Cowburn, Toshihisa Tanaka, Bengt Winblad, Wen-Lin An, Irina Alafuzoff, Heiko Braak, Ichiro Tsujio |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Blotting Western Tau protein tau Proteins Protein Serine-Threonine Kinases Pathology and Forensic Medicine Glycogen Synthase Kinase 3 Cellular and Molecular Neuroscience Alzheimer Disease GSK-3 Proto-Oncogene Proteins medicine Humans Phosphorylation Glycogen synthase Protein kinase A Protein kinase B Aged Aged 80 and over Microscopy Confocal biology Brain Neurofibrillary Tangles Neurofibrillary tangle Middle Aged medicine.disease Immunohistochemistry Isoenzymes Huntington Disease biology.protein Neurology (clinical) Alzheimer's disease Proto-Oncogene Proteins c-akt |
| Zdroj: | Acta Neuropathologica. 105:381-392 |
| ISSN: | 1432-0533 0001-6322 |
| DOI: | 10.1007/s00401-002-0657-y |
| Popis: | Protein kinase B (PKB) is an important intermediate in the phosphatidylinositol-3 kinase signaling cascade that acts to phosphorylate glycogen synthase kinase-3 (GSK-3) at its serine 9 residue, thereby inactivating it. Activated GSK-3 has been previously shown to be preferentially associated with neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brain. In the present study, we performed immunohistochemistry with an antibody to the active form of PKB in brains with different stages of neurofibrillary degeneration. We found that the amount of activated PKB (p-Thr308) increased in correlation to the progressive sequence of AT8 immunoreactivity and neurofibrillary changes assessed according to Braak's criteria. By confocal microscopy, activated PKB (p-Thr308) was found to appear in particular in neurons that are known to later develop NFTs in AD. Western blotting showed that activated PKB was increased by more than 50% in the 16,000- g supernatants of AD brains as compared with normal aged and Huntington's disease controls. This increase in PKB levels corresponded with a several-fold increase in the levels of total tau and abnormally hyperphosphorylated tau at the Tau-1 site. These studies suggest the involvement of PKB/GSK-3 signaling in Alzheimer neurofibrillary degeneration. |
| Databáze: | OpenAIRE |
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