Beyond amyloid:altered cell cycle regulation in Alzheimer's disease:comparison of P21 signaling in patients lymphocytes and brain neurons

• Autorzy: Mietelska-Porowska A. , Wojsiat J. , Laskowska-Kaszub K. , Stepien T. , Wierzba-Bobrowicz T. , Wojda U.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Alzheimer’s disease (AD) develops for decades, but the molecular mechanism of pathogenesis is poorly understood. In result, an effective AD cure is still missing. According to the cell cycle (CC) hypothesis, one of the AD causes is CC reactivation in mature neurons. We aimed at elucidation if similar CC alterations occur in AD brain neurons and in peripheral blood cells. METHODS: As the study materials, we used 40 lines of immortalized lymphoblasts from sporadic AD (SAD) patients and 40 lines from healthy non-demented individuals (controls)1-4. CC in lymphocytes was analyzed by real-time PCR-arrays, immunoblotting, and flow cytometry. Human post mortem brain tissue from AD patients was prepared by paraffin embedding and microscopic tissue slides of hippocampus and enthorinal cortex was analyzed by antip21 immunohistochemical staining. RESULTS: Our data demonstrated aberrant CC in SAD lymphoblasts that involved a prolongation of the G1 phase driven by a marked increase of levels of p21 protein (Walf1/Cip1/Sid1), the key regulator of the G1/S CC checkpoint and of apoptosis. Consistently, we also found differences in p21 levels and its signaling pathway in apoptotic response of SAD lymphoblasts to redox stess. The analysis of p21 protein levels and related signaling in AD brain neurons will also be presented. CONCLUSIONS: In summary, these studies indicate that p21-related molecular changes underlie altered cell cycle and apoptosis in AD pathology and may represent novel therapeutic targets. Moreover, our data show that AD have a features of a systemic disease with CC alterations in peripheral lymphoblasts which thus have a potential diagnostic value. Support: CEPT, Polish National Science Centre grant NN401 596840, and JPND grant 2/BIOMARKAPD/JPND/2012.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S38-S39

Twórcy

autor

Mietelska-Porowska A.

• Laboratory of Preclinical Studies of Higher Standard, Neurobiology Center, Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Wojsiat J.

• Laboratory of Preclinical Studies of Higher Standard, Neurobiology Center, Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Laskowska-Kaszub K.

• Laboratory of Preclinical Studies of Higher Standard, Neurobiology Center, Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Stepien T.

• Laboratory of Preclinical Studies of Higher Standard, Neurobiology Center, Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Wierzba-Bobrowicz T.

• Department of Neuropathology, Institute of Psychiatry and Neurology, Warsaw, Poland

autor

Wojda U.

• Laboratory of Preclinical Studies of Higher Standard, Neurobiology Center, Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland