Cell cycle activation in striatal neurons from Huntington's disease patients and rats treated with 3‐nitropropionic acid

Abstract

This study was undertaken to investigate the potential role of cell cycle re-entry in an experimental model of Huntington's disease and in human brain samples. We found that after treatment of rats with the mitochondrial neurotoxin 3-nitropropionic acid, the expression of cell cycle markers of G1 phase measured by immunohistochemistry was induced in the striatal brain region. Furthermore, we detected an increase in the nuclear and also cytoplasmatic E2F-1 expression, suggesting that this protein could activate the apoptotic cascade in rat brain. Western blot analysis of post-mortem brain samples from patients also showed an increase in the expression of E2F-1 and cyclin D1 in comparison with control samples. These results indicate that cell cycle re-entry is activated in Huntington's disease and may contribute to the neurodegenerative process.

Cell Cycle Activation and CNS Injury

“…There are many observations that seem to confirm the hypothesis that re-entry in the cell cycle is a convergence point in many neurodegenerative diseases, as well as in acute CNS injuries leading to neuronal cell death (Pelegri et al 2008). Furthermore, cell cycle activation is involved in the development of neurotoxic phenotype in key CNS cell types such as astrocytes and microglia.…”

“…Considering that cell loss progresses over decades in PD patients, the high rate of aneuploidy observed indicate that affected neurons may persist for a long time in a G2 arrested state before dying. CCE are also found in the brains of HD patients (Pelegri et al 2008).…”

成熟神经元的细胞周期再活化与大脑可塑性、 神经元损伤和神经退行性疾病的关系

“…More recently, using microarray analysis in single motor neuron in the SOD1 transgenic murine model of familial ALS, researchers found a significant increase in the expression of cyclins D2, E2, and I [86] . Finally, over- expression of cyclin D1 and the transcription factor E2F1 in striatal neurons has also been described in Huntington's disease [87] .…”

Activation of ataxia telangiectasia muted under experimental models and human Parkinson’s disease

“…in vitro and also in vivo [16,19]. Moreover, CDK inhibitors have neuroprotective effects in a wide range of experimental neurodegeneration models, and studies performed using the brains of patients suffering from neurodegenerative diseases such as PD, AD, and Huntington's disease have demonstrated an increase in the expression of proteins involved in the cell cycle [21][22][23][24][25][26][27][28][29][30][31]. Interestingly, the possible link between cell-cycle re-entry and neuronal apoptosis could be the transcription factor E2F-1 [32,33].…”