Differential Activation of mTOR Complex 1 Signaling in Human Brain with Mild to Severe Alzheimer's Disease
| Autor: | David A. Greenberg, Yong Xin Sun, Lin Xie, Jianping Jia, XiaoOu Mao, Xunming Ji, Veronica Galvan, Kunlin Jin |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cell signaling Hippocampus Nerve Tissue Proteins mTORC1 Mechanistic Target of Rapamycin Complex 1 Biology Hippocampal formation mTORC2 Young Adult Alzheimer Disease medicine Animals Humans PI3K/AKT/mTOR pathway Aged Aged 80 and over Psychiatric Status Rating Scales TOR Serine-Threonine Kinases General Neuroscience General Medicine Human brain Blot Psychiatry and Mental health Clinical Psychology medicine.anatomical_structure Gene Expression Regulation Multiprotein Complexes Postmortem Changes Cancer research Female Geriatrics and Gerontology Cognition Disorders Neuroscience Signal Transduction |
| Zdroj: | Journal of Alzheimer's Disease. 38:437-444 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-131124 |
| Popis: | Mammalian target of rapamycin (mTOR) signaling has been suggested to be effective in modifying cognitive status in animal models of Alzheimer's disease (AD), but little is known about its role in AD patients. We hereby tested whether mTOR signaling was activated and whether activated mTOR signaling was related to the degree of cognitive deficits in patients with AD. Autopsy brain hippocampal tissues were obtained from controls and patients with AD and Western blots were performed using antibodies against mTOR signaling molecules and RagC, an upstream component of mTOR complex 1 (mTORC1) signaling. We found that expression of mTOR/p-mTOR and its downstream targets S6/p-S6 and Raptor/p-Raptor were expressed in the control and AD hippocampus. The expression levels of these signaling molecules were significantly increased in the hippocampus at the severe stages of AD, compared to controls and other stages of AD. Interestingly, Rictor expression level was unaltered. In addition, RagC was increased in the hippocampus at the early, moderate, and severe stages of AD. Our data indicate that mTORC1, but not mTORC2, was activated in the AD brains and that the level of mTOR signaling activation was correlated with cognitive severity of AD patients. |
| Databáze: | OpenAIRE |
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