RNAi mediated silencing of cyclin-dependent kinases of G1 phase slows down the cell-cycle progression and reduces apoptosis

• Autorzy: Sierant M. , Piotrzkowska D. , Nawrot B.
• Języki publikacji: EN

Abstrakty

EN

One of the hypotheses on the origin of Alzheimer's disease (AD) stems from a close relation between a re-activation of a cell-cycle in post-mitotic neurons and a neural cells death observed in pathologically affected parts of AD brains. In the normal, healthy brain almost all neural cells are terminally differentiated and "locked" in the GO phase of the cell-cycle. For these cells, the consequence of the re-entry to the cell-cycle is targeting them towards cellular divisions and turning on the apoptotic pathway. We used an RNA interference (RNAi) methodology in neural cells to switch-off genes for two cyclin- dependent kinases 4 and 6 (cdk4, cdk6), which control the activation of the initial steps of the cell-cycle. As a result, some evidences are delivered that silencing these genes, which are expressed during cell proliferation but inhibited at mature neurons, prevents the stimulation of apoptotic pathways in the neural cells cultured in a oxidative stress conditions and may have a neuroprotective effect. We demonstrate that down-regulation of genes important in the G1 phase of the cell-cycle may play the protective function on the neuronal cells, and can be considered as the promising approach for the potential gene therapy of neurodegenerative diseases.

Słowa kluczowe

EN

RNAi; siRNA; human disease; Alzheimer's disease; cyclin-dependent kinase; G1 phase; cell cycle; progression; apoptosis; brain; neurodegenerative disease; memory loss

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: 1
• Opis fizyczny: p.36-47,fig.,ref.

Twórcy

autor

Sierant M.

• Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland

autor

Piotrzkowska D.

• Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland

autor

Nawrot B.

• Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland

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