TAILIEUCHUNG - Báo cáo khoa học: Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer’s disease brain

The pathogenesis of formation of neurofibrillary tangles (NFTs) in Alzhei-mer’s disease (AD) brains is unknown. One of the possibilities might be that translation of tau mRNA is aberrantly regulated in AD brains. In the current study, levels of various translation control elements including total and phosphorylated (p) forms of mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), eukaryotic elon-gation factor 2 (eEF2), and eEF2 kinase were investigated in relationship with tau in homogenates of the medial temporal cortex from 20 AD and 10 control brains. . | ềFEBS Journal Levels of mTOR and its downstream targets 4E-BP1 eEF2 and eEF2 kinase in relationships with tau in Alzheimer s disease brain Xu Li1 Irina Alafuzoff2 Hilkka Soininen3 Bengt Winblad1 and Jin-Jing Pei1 1 Division of ExperimentalGeriatrics Department of Neurotec Karolinska Institutet Huddinge Sweden 2 Department of Neuroscience and Neurology Kuopio University Hospital Kuopio University Finland 3 Department of Neurology and Neuroscience and Neurology Kuopio University Hospital Kuopio University Finland Keywords 4E-BP1 Alzheimer s disease mTOR translation control tau Correspondence . Pei Karolinska Institutet Department of Neurotec Division of Experimental Geriatrics KFC Plan 4 Novum S-141 86 Huddinge Sweden Fax 46 858583880 Tel 46 858583751 E-mail Received 21 April2005 revised 17 June 2005 accepted 24 June 2005 doi The pathogenesis of formation of neurofibrillary tangles NFTs in Alzheimer s disease AD brains is unknown. One of the possibilities might be that translation of tau mRNA is aberrantly regulated in AD brains. In the current study levels of various translation control elements including total and phosphorylated p forms of mammalian target of rapamycin mTOR eukaryotic initiation factor 4E binding protein 1 4E-BP1 eukaryotic elongation factor 2 eEF2 and eEF2 kinase were investigated in relationship with tau in homogenates of the medial temporal cortex from 20 AD and 10 control brains. We found that levels of p-mTOR Ser2481 and p-4E-BP1 Thr70 and Ser65 dramatically increase in AD and are positively significantly correlated with total tau and p-tau. Levels of p-eEF2K were significantly increased and total eEF2 significantly decreased in AD when compared to controls. The changes of p-mTOR 2481 p-4E-BP1 and p-eEF2 were immunohistochemically confirmed to be in neurons of AD brains. This suggested that there are obvious abnormalities of elements related with translation control in AD brain .

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