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Apoptosis has been implicated in many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We previously demonstrated a role for G1 to S phase cell cycle regulators in ALS with increased levels of hyperphosphorylated retinoblastoma (ppRb) and E2F-1 in ALS spinal cord motor neurons. In this study we examined the levels of the cell cycle checkpoint tumor suppressor protein p53 with concurrent changes in cell death markers during ALS. Expression and subcellular distribution of p53, retinoblastoma, Bax, Fas, and caspases were explored by immunoblot, immunohistochemistry and double-label confocal microscopy in the spinal cord and motor cortex of ALS and control subjects. We identified elevated levels of p53 in ALS spinal cord motor neurons but not neurons in the motor cortex. In addition, there was an increase in Bax, Fas, caspases-8 and -3 proteins in ALS spinal motor neurons. While caspase-3 and TUNEL labeled neurons were positive for ppRb, E2F-1 and p53 in spinal motor neurons, and Fas co-localized with caspase-8 in spinal motor neurons, we failed to observe these results in large neurons in the motor cortex of ALS subjects. We have linked p53 and activation of G1 to S phase cell cycle regulators to an apoptotic mode of cell death ALS spinal cord motor neurons.

p53 and Cell Cycle Proteins Participate in Spinal Motor Neuron Cell Death in ALS~!2010-02-16~!2010-02-19~!2010-04-14~!