| Title | P53-Mediated G(1)/S Checkpoint Dysfunction in Lymphocytes from Alzheimer's disease patients. | | Author(s) | Zhou X, Jia J | | Institution | Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China; Key Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China. | | Source | Neurosci Lett 2009 Nov 12. | | Abstract | To date, Alzheimer disease (AD) is still difficult to be diagnosed in its earliest stage. The cell cycle aberrations may be the earliest neuropathological events detected in AD thus far. The cell cycle regulatory failure in AD occurring at "G(1)/S transition checkpoint" which is mediated by the tumor suppressor protein p53 has been identified. Herein, we observed the response of activated lymphocytes to G(1)/S transition blocker to assess the G(1)/S checkpoint function and the p53 conformation state adopted in lymphocytes from AD patients and healthy non-AD controls. We found that the activiated lymphocytes from AD patients were less sensitive to G(1)/S transition blocker than those from controls, indicating that the G(1)/S checkpoint failed to function well in AD lymphocytes. In addition, AD cells specifically expressed an anomalous conformationally mutant-like p53 that made these cells distinct from lymphocytes of controls. We speculated that the altered conformational p53 probably be responsible for G(1)/S checkpoint dysfunction in AD cells. Our hypothesis was supported by the results that G(1)/S checkpoint dysfunction was not restricted to neurons in AD patients, but also occured in peripheral lymphocytes. Two pontential biomarkers were indicated in blood lymphocytes from AD patients: the G(1)/S checkpoint dysfunction and the conformationally mutant-like p53 protein. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19914341 |
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